Gene interactions and pathways from curated databases and text-mining

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MLST8 — MTOR

Pathways - manually collected, often from reviews:

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

Text-mined interactions from Literome

Zhang et al., Ann Surg Oncol 2011 (Colorectal Neoplasms) : Additionally, Indo and Nim could reduce the mTOR signaling activity after COX-2 silencing in CRC cells
Murata et al., J Biol Chem 2011 (Neuroblastoma...) : A new cytosolic pathway from a Parkinson disease associated kinase, BRPK/PINK1 : activation of AKT via mTORC2
Baum et al., Am J Physiol Endocrinol Metab 2009 : Compared with control livers, insulin stimulated Akt phosphorylation and mTORC1 signaling, as assessed by increased phosphorylation of the mTORC1 targets eIF4E binding protein ( 4E-BP ) 1 and ribosomal protein S6 kinase (S6K)1, and promoted assembly of the eIF4G x eIF4E complex ... Overall, the results suggest that glucagon acts in a dominant manner to repress insulin induced mTORC1 signaling, which is in contrast to previous studies showing a dominant action of insulin in the control of hepatic gluconeogenesis ... Overall, the results suggest that glucagon acts in a dominant manner to repress insulin induced mTORC1 signaling, which is in contrast to previous studies showing a dominant action of insulin in the control of hepatic gluconeogenesis
Le Bacquer et al., J Endocrinol 2013 (Hyperglycemia) : mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells ... mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells
Han et al., Cell Signal 2008 (Tuberous Sclerosis) : Pam ( Protein associated with Myc ) functions as an E3 ubiquitin ligase and regulates TSC/mTOR signaling
Acosta-Jaquez et al., Mol Cell Biol 2009 : These data provide the first evidence that site-specific mTOR phosphorylation regulates mTORC1 function and suggest a model whereby insulin stimulated mTOR S1261 phosphorylation promotes mTORC1 autokinase activity, substrate phosphorylation, and cell growth
Wu et al., Proc Natl Acad Sci U S A 2012 : However, excessive miR-17-92 expression enhances mammalian target of rapamycin (mTOR) signaling and strongly skews the differentiation toward short lived terminal effector cells
Hsu et al., Science 2011 : The adaptor protein Grb10 was identified as an mTORC1 substrate that mediates the inhibition of phosphoinositide 3-kinase typical of cells lacking tuberous sclerosis complex 2 (TSC2) , a tumor suppressor and negative regulator of mTORC1
Lodeiro et al., PloS one 2009 : This beta-arrestin scaffolded complex leads to full activation of Akt through PDK1 and mTORC2 , which are not associated to the complex
Agarwal et al., Oncogene 2013 : We found that a suppression of RhoGDI2 by rictor is not related to the Sin1 or raptor function that excludes a role of mTORC2 or mTORC1 in regulation of RhoGDI2 ... We found that a suppression of RhoGDI2 by rictor is not related to the Sin1 or raptor function that excludes a role of mTORC2 or mTORC1 in regulation of RhoGDI2
Wang et al., Biochem Biophys Res Commun 2012 (Vitreoretinopathy, Proliferative) : TNF-a promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling ... In conclusion, this study suggest that TNF-a promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1 , but not mTORC2 signaling ... In conclusion, this study suggest that TNF-a promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling
Regazzetti et al., PloS one 2012 (MAP Kinase Signaling System) : In 3T3-L1 adipocytes, silencing of REDD1 with siRNA induces an increase of mTORC1 activity as well as an inhibition of insulin signaling pathway and lipogenesis
Wang et al., Oncogene 2008 (Prostatic Neoplasms) : Inhibition of both mTORC1 and mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1, but not mTORC2 ... Inhibition of both mTORC1 and mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1, but not mTORC2 ... Inhibition of both mTORC1 and mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1 , but not mTORC2 ... Inhibition of both mTORC1 and mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1 , but not mTORC2
Prabhu et al., Oncogene 2007 (Leukemia, Myelogenous, Chronic, BCR-ABL Positive) : In this study, we found that both Bcr-Abl and the rapamycin-sensitive mTORC1 complex contribute to the phosphorylation ( inactivation ) of 4E-BP1 , an inhibitor of the eIF4E translation initiation factor ... Experiments with rapamycin and the Bcr-Abl inhibitor, imatinib mesylate, in Bcr-Abl expressing cell lines and primary CML cells indicated that Bcr-Abl and mTORC1 induced formation of the translation initiation complex, eIF4F
Lian et al., J Biol Chem 2012 : Furthermore, inhibition of PI3K/Akt/mTOR signaling , but not canonical Smad signaling, downstream of TGFß, blocked TGFß induced synthesis of vimentin , and inhibited ATF4 dependent Ocn transcription in osteoblasts
Kumar et al., Diabetes 2010 : To determine the physiological role of rictor/mTORC2 in insulin signaling and action in fat cells, we developed fat cell-specific rictor knockout ( FRic ( -/- ) ) mice
Vadysirisack et al., Methods Mol Biol 2012 : Our work has demonstrated that the stress induced protein REDD1 is essential for hypoxia regulation of mTORC1 activity and has further defined the molecular mechanism whereby REDD1 represses mTORC1 activity under hypoxic stress ... Our work has demonstrated that the stress induced protein REDD1 is essential for hypoxia regulation of mTORC1 activity and has further defined the molecular mechanism whereby REDD1 represses mTORC1 activity under hypoxic stress
Lee et al., Carcinogenesis 2010 (Colonic Neoplasms) : In contrast, the Akt dependent mTORC1 inhibition by selenium did not require AMPKalpha ( 1 )
Lamming et al., Science 2012 (Insulin Resistance) : We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin mediated suppression of hepatic gluconeogenesis
Yao et al., Science signaling 2013 : BSTA promotes mTORC2 mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation ... The mammalian target of rapamycin complex 2 ( mTORC2 ) facilitated the phosphorylation of BSTA and its association with Akt1, and the BSTA-Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser473 in response to growth factor stimulation ... The mammalian target of rapamycin complex 2 ( mTORC2 ) facilitated the phosphorylation of BSTA and its association with Akt1, and the BSTA-Akt1 interaction promoted the association of mTORC2 with Akt1 and phosphorylation of Akt1 at Ser473 in response to growth factor stimulation
Haslinger et al., Biol Reprod 2013 : Accordingly, a decrease in EGF stimulated phosphorylation of AKT ( Ser473 and Thr308 ) and its downstream target mTORC1 ( Ser2448 ) was noticed in AKT1 and AKT3 shRNAmir cell pools
Fonseca et al., Biochem J 2008 : The binding of PRAS40 to 14-3-3 proteins is not required for activation of mTORC1 signalling by phorbol esters/ERK
Ng et al., Cell Death Differ 2012 : However, AMPK activation represses the mTOR complex-1 (mTORC1) pathway only in transformed cells, suggesting a key role for AMPK mediated mTORC1 inhibition in the suppression of anoikis ... Our data implicate AMPK mediated mTORC1 inhibition and suppression of protein synthesis as a means for bioenergetic conservation during detachment, thus promoting anoikis resistance
Bridges et al., Mol Biol Cell 2012 : In this paper, we show that PIKFYVE and PI3K-C2a are necessary for activation of mTORC1 and its translocation to the plasma membrane in 3T3-L1 adipocytes ... In this paper, we show that PIKFYVE and PI3K-C2a are necessary for activation of mTORC1 and its translocation to the plasma membrane in 3T3-L1 adipocytes
Fang et al., Curr Biol 2003 : PLD1 regulates mTOR signaling and mediates Cdc42 activation of S6K1 ... Our observations reveal the involvement of PLD1 in mTOR signaling and cell size control, and provide a molecular mechanism for Cdc42 activation of S6K1
Tillu et al., Molecular pain 2012 (Acute Pain...) : We reasoned that activators of AMP activated protein kinase (AMPK) may represent a novel treatment avenue for the local treatment of incision induced pain because AMPK activators inhibit ERK and mTOR signaling , two important pathways involved in the sensitization of peripheral nociceptors
Melnik , Hautarzt 2013 (Acne Vulgaris...) : mTORC1 , the central hub of protein- and lipid biosynthesis, cell growth and proliferation, is activated by insulin, IGF-1 and branched-chain essential amino acids, especially leucine ... mTORC1 , the central hub of protein- and lipid biosynthesis, cell growth and proliferation, is activated by insulin, IGF-1 and branched-chain essential amino acids, especially leucine ... mTORC1 , the central hub of protein- and lipid biosynthesis, cell growth and proliferation, is activated by insulin , IGF-1 and branched-chain essential amino acids, especially leucine
Kim et al., Mol Cell Biol 2008 : Subsequent studies established that GIP increased the nuclear localization of TORC2 and phosphorylation of CREB serine 133 through a pathway involving PKA activation and reduced AMPK phosphorylation ... The antiapoptotic effect of GIP in beta cells is therefore partially mediated through a novel mode of transcriptional regulation of Bcl-2 involving cAMP/PKA/AMPK dependent regulation of CREB/TORC2 activity ... The antiapoptotic effect of GIP in beta cells is therefore partially mediated through a novel mode of transcriptional regulation of Bcl-2 involving cAMP/PKA/AMPK dependent regulation of CREB/TORC2 activity
Rao et al., Immunity 2012 : The Foxo1 inactivation was dependent on mTORC1 kinase, given that blockade of mTORC1 abrogated mTORC2 mediated Akt ( Ser473 ) kinase phosphorylation, resulting in Foxo1 dependent switch from T-bet to Eomesodermin transcription factor activation and increase in memory precursors ... The Foxo1 inactivation was dependent on mTORC1 kinase, given that blockade of mTORC1 abrogated mTORC2 mediated Akt ( Ser473 ) kinase phosphorylation, resulting in Foxo1 dependent switch from T-bet to Eomesodermin transcription factor activation and increase in memory precursors
Ikeda et al., J Pharmacol Sci 2013 (Adrenal Gland Neoplasms...) : Indeed, direct mTORC1 inhibition initiates ULK1/2 autophosphorylation and subsequent Atg13 and FIP200 phosphorylation, inducing autophagy ... Indeed, direct mTORC1 inhibition initiates ULK1/2 autophosphorylation and subsequent Atg13 and FIP200 phosphorylation, inducing autophagy
Boletta , PathoGenetics 2009 : The mTORC1 complex regulates cell growth ( size ), proliferation, translation and autophagy, and mTORC2 regulates the actin cytoskeleton and apoptosis
Esen et al., Cell Metab 2013 : Deletion of Lrp5 in the mouse, which decreases postnatal bone mass, reduces mTORC2 activity and glycolytic enzymes in bone cells and lowers serum lactate levels
Lee et al., Genes Dev 2010 : Collectively, these findings establish mTOR/rictor mediated Akt activation as a key driver of NSC proliferation and gliogenesis, and identify a unique mechanism for conferring brain region-specific responses to cancer causing genetic changes
Liu et al., Proc Natl Acad Sci U S A 2011 (Hypertelorism...) : Increased PP2A levels, resulting from proteasome inhibition or depletion of MID1, lead to disruption of the mTOR/Raptor complex and down-regulated mTORC1 signaling
Wang et al., J Biol Chem 2008 : Furthermore, FKBP38 did not inhibit mTORC1 signaling ... Reducing TCTP levels did not reproducibly affect mTORC1 signaling in amino acid-replete/insulin stimulated cells ... Our data also indicate that, in the mammalian cell lines tested here, neither TCTP nor FKBP38 regulates mTORC1 signaling ... Our data also indicate that, in the mammalian cell lines tested here, neither TCTP nor FKBP38 regulates mTORC1 signaling
Chakrabarti et al., Diabetes 2010 : Activation of mTORC1 signaling in 3T3-L1 adipocytes by ectopic expression of Rheb inhibits expression of ATGL and HSL at the level of transcription, suppresses lipolysis, increases de novo lipogenesis, and promotes intracellular accumulation of triglycerides ... Activation of mTORC1 signaling in 3T3-L1 adipocytes by ectopic expression of Rheb inhibits expression of ATGL and HSL at the level of transcription, suppresses lipolysis, increases de novo lipogenesis, and promotes intracellular accumulation of triglycerides
Zeng et al., Blood 2007 (Leukemia, Myeloid, Acute) : Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML
Treins et al., Oncogene 2010 : Rictor phosphorylation at Thr1135 does not lead to major changes in mTORC2-kinase activity
Han et al., Cell 2012 : Here we show that leucyl-tRNA synthetase (LRS) plays a critical role in amino acid induced mTORC1 activation by sensing intracellular leucine concentration and initiating molecular events leading to mTORC1 activation
Kimball et al., J Biol Chem 2008 : Rapid turnover of the mTOR complex 1 (mTORC1) repressor REDD1 and activation of mTORC1 signaling following inhibition of protein synthesis
Kim et al., J Lipid Res 2010 : GIP induced phospho-CREB and TORC2 were shown to bind to a cAMP-response element ( -II ) site in the human LPL promoter and GIP increased protein-protein interactions of these two factors ... The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK dependent CREB/TORC2 activation ... The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK dependent CREB/TORC2 activation ... The lipogenic effects of GIP in the presence of insulin are therefore at least partially mediated by upregulation of adipocyte LPL gene transcription through a pathway involving PI3-K/PKB/AMPK dependent CREB/TORC2 activation
Matheny et al., Growth Factors 2012 : Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110ß-deficient myoblasts is mediated by PI3K p110a and mTORC2
Park et al., Leukemia 2013 (Leukemia, Myeloid, Acute...) : We conducted a phase Ib trial combining RAD001 ( everolimus ), an allosteric inhibitor of mTORC1 , and conventional chemotherapy, in AML patients under 65 years of age at first relapse ( clinical trial NCT 01074086 )
Maru et al., J Urol 2013 (Carcinoma, Renal Cell...) : We investigated whether mTORC2 regulates E-cadherin expression and controls cell motility during HIF-2a down-regulation in renal cell carcinoma cells ... Results show that mTORC2 might regulate E-cadherin expression and suppress cell motility by controlling the mTORC2-HIF-2a signaling pathway
Urbanska et al., J Biol Chem 2012 : We also identified Akt as a downstream effector of mTORC2 needed for proper dendritic arbor morphology, the action of which required mTORC1 and p70S6K1
Zhao et al., Anat Rec (Hoboken) 2011 (Nasopharyngeal Neoplasms) : AMPK mediated inhibition of mTORC1 signaling may be involved in this process
Gustafson et al., Oncogene 2010 : Phosphorylation of Myc proteins is controlled in-part by the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt/mTOR signaling , with additional contributions from Aurora A kinase
Kurebayashi et al., Cell reports 2012 : Inhibition of PI3K-Akt-mTORC1-S6K1 axis impairs the downregulation of Gfi1 , a negative regulator of Th17 differentiation
Tatebe et al., Curr Biol 2010 : Human Rab6 can substitute Ryh1 in S. pombe, and therefore Rab6 may be a potential activator of TORC2 in mammals
Han et al., J Biol Chem 2012 : Our results establish that Pam regulates TSC/mTOR signaling in vitro and in vivo through two distinct domains
Dormond et al., J Immunol 2008 (Inflammation...) : CD40 induced signaling in human endothelial cells results in mTORC2- and Akt dependent expression of vascular endothelial growth factor in vitro and in vivo ... Also, rapamycin failed to inhibit VEGF promoter activation, as well as VEGF protein expression in EC transfected with a constitutively active construct of Akt, further demonstrating that mTORC1 is not necessary for CD40- and Akt induced expression of VEGF
Wu et al., Urol Oncol 2012 (Carcinoma, Transitional Cell...) : The present findings also suggest rictor dependent AKT activation as a consequence of mTORC1 inhibition
Yoon et al., J Biol Chem 2011 : This leads to PA antagonizing FKBP38 inhibition of mTORC1 kinase activity in vitro and rescuing mTORC1 signaling from FKBP38 in cells
Le Borgne et al., PloS one 2013 (Listeriosis...) : Absence of kinase suppressor of Ras 1 (KSR1), a scaffold protein of the ERK signaling pathway, or inhibition of ERK resulted in decreased mTORC1 activity following T cell activation ... Absence of kinase suppressor of Ras 1 (KSR1) , a scaffold protein of the ERK signaling pathway, or inhibition of ERK resulted in decreased mTORC1 activity following T cell activation
Hwang et al., BMB Rep 2011 (Ischemia) : The loss of TSC2, which is upstream of mTOR, activates S6K1 , promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2 , which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt ... The loss of TSC2 , which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt
Pajvani et al., Nat Med 2013 (Body Weight...) : We demonstrate that Notch signaling increases mTorc1 complex stability, augmenting mTorc1 function and sterol regulatory element binding transcription factor 1c ( Srebp1c ) -mediated lipogenesis
Piao et al., Biochem Biophys Res Commun 2009 : Reciprocally, the mTORC1 dependent phosphorylation of FLCN was reported
Thiem et al., J Clin Invest 2013 (Disease Models, Animal...) : We analyzed the mechanism of GP130 mediated mTORC1 activation in cells and mice and revealed a requirement for JAK and PI3K activity but not for GP130 tyrosine phosphorylation or STAT3
Wu et al., J Biol Chem 2011 : The p38ß-PRAK cascade targets Rheb to inhibit mTORC1 activity upon glucose depletion ... The phosphorylation of Raptor on these sites enhances mTORC1 activity, and contributes largely to arsenite induced mTORC1 activation ... The phosphorylation of Raptor on these sites enhances mTORC1 activity, and contributes largely to arsenite induced mTORC1 activation
Ost et al., Mol Med 2010 (Diabetes Mellitus, Type 2...) : Conversely, mitochondrial dysfunction attenuated insulin activation of mTORC1 , enhanced autophagy and attenuated feedback to IRS1
Yecies et al., Cell Metab 2011 : To further define the role of mTORC1 in the regulation of SREBP1c in the liver, we generated mice with liver-specific deletion of TSC1 ( LTsc1KO ), which results in insulin independent activation of mTORC1 ... Therefore, mTORC1 activation is not sufficient to stimulate hepatic SREBP1c in the absence of Akt signaling, revealing the existence of an additional downstream pathway also required for this induction
Espona-Fiedler et al., Biochem Pharmacol 2012 (Melanoma) : The inhibition of mTORC1 and mTORC2 complexes by PG or OBX resulted in a loss of AKT phosphorylation at S473, preventing its full activation, with no significant effect on T308 ... The inhibition of mTORC1 and mTORC2 complexes by PG or OBX resulted in a loss of AKT phosphorylation at S473, preventing its full activation, with no significant effect on T308
Lee et al., Immunity 2010 : mTORC2 promoted phosphorylation of protein kinase B ( PKB, or Akt ) and PKC, Akt activity, and nuclear NF-kappaB transcription factors in response to T cell activation
Liu et al., J Biol Chem 2010 : Taken together, our studies reveal that RSV inhibits leucine stimulated mTORC1 activation by promoting mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity ... Taken together, our studies reveal that RSV inhibits leucine stimulated mTORC1 activation by promoting mTOR/DEPTOR interaction and thus uncover a novel mechanism by which RSV negatively regulates mTOR activity
Lipinski et al., Dev Cell 2010 (MAP Kinase Signaling System) : In a genome-wide human siRNA screen, we demonstrate that under normal nutrient conditions upregulation of autophagy requires the type III PI3 kinase, but not inhibition of mTORC1 , the essential negative regulator of starvation induced autophagy
Zhao et al., Mol Cell 2011 : DEPTOR , an inhibitor of mTORC1 and mTORC2 , is degraded via ubiquitin-proteasome pathway by an unknown E3 ubiquitin ligase ... DEPTOR , an inhibitor of mTORC1 and mTORC2, is degraded via ubiquitin-proteasome pathway by an unknown E3 ubiquitin ligase
Wang et al., J Biol Chem 2007 : In response to insulin and nutrients, mTORC1 , consisting of mTOR, raptor ( regulatory associated protein of mTOR ), and mLST8, is activated and phosphorylates eukaryotic initiation factor 4E-binding protein ( 4EBP ) and p70 S6 kinase to promote protein synthesis and cell size
Dibble et al., Mol Cell Biol 2009 : We find that Rictor-T1135 is directly phosphorylated by the mTORC1 dependent kinase S6K1 ... Although this phosphorylation event does not affect mTORC2 integrity or in vitro kinase activity, expression of a phosphorylation site mutant of Rictor ( T1135A ) in either wild-type or Rictor null cells causes an increase in the mTORC2 dependent phosphorylation of Akt on S473 ... However, Rictor-T1135 phosphorylation does not appear to regulate mTORC2 mediated effects on SGK1 or PKC alpha ... However, Rictor-T1135 phosphorylation does not appear to regulate mTORC2 mediated effects on SGK1 or PKC alpha
Csibi et al., Cell 2013 (Neoplasms) : Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome mediated destabilization of cAMP-responsive element binding 2 ( CREB2 )
Averous et al., Oncogene 2008 (Breast Neoplasms) : Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1
Mazhab-Jafari et al., Structure 2012 : We demonstrate that the opposing functions of Tyr35 in the intrinsic and GAP stimulated GTP catalysis are critical for optimal mTORC1 regulation
Chai et al., Peptides 2010 : MC4R activation potentiates insulin stimulated mTOR signaling via the AMPK pathway
White et al., Am J Physiol Endocrinol Metab 2013 (Cachexia...) : Muscle mTORC1 suppression by IL-6 during cancer cachexia : a role for AMPK ... How IL-6 can induce suppression of mTORC1 signaling remains to be established
Rothbart et al., Cancer Res 2010 : Whereas AMPK activation resulted in marked inhibition of mTORC1 , other targets of AMPK were phosphorylated that were not mTORC1 dependent
Koyanagi et al., PloS one 2011 : Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells ... Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells
Shu et al., Mol Biol Cell 2012 : Synthesis of cAMP receptor and adenylyl cyclase A ( ACA ) is inhibited, and activation of ACA, RasC, and RasG, phosphorylation of extracellular signal regulated kinase 2 , activation of TORC2 , and stimulation of actin polymerization and myosin assembly are greatly reduced ... Synthesis of cAMP receptor and adenylyl cyclase A ( ACA ) is inhibited, and activation of ACA, RasC, and RasG, phosphorylation of extracellular signal regulated kinase 2, activation of TORC2 , and stimulation of actin polymerization and myosin assembly are greatly reduced
Castets et al., Cell Metab 2013 : In young TSCmKO mice, constitutive and starvation induced autophagy is blocked at the induction steps via mTORC1 mediated inhibition of Ulk1 , despite FoxO3 activation
Ethier et al., PloS one 2012 (Necrosis) : In this study, we show that PARP-1 activation and PAR synthesis affect the energetic status of cells, inhibit the mTORC1 signaling pathway and possibly modulate the mTORC2 complex affecting cell fate
Rosel et al., J Cell Sci 2012 : TORC1 is required for growth in response to growth factors, nutrients and the cellular energy state ; TORC2 regulates AKT signaling, which can modulate cytoskeletal polarization
Astle et al., Oncogene 2012 (Cell Transformation, Neoplastic) : We demonstrate that AKT induced senescence is p53 dependent and is characterised by mTORC1 dependent regulation of p53 translation and stabilisation of p53 protein following nucleolar localisation and inactivation of MDM2
Vu et al., Clin Cancer Res 2010 (Leukemia...) : The majority of preclinical and clinical efforts to target TOR have involved using rapamycin and its analogs ( rapalogs ), which suppress TORC1 only partially and do not acutely inhibit TORC2
Kato et al., PloS one 2013 : Knockdown of Raptor , a positive regulator of mTORC1 , also had the similar effect ... Knockdown of TSC2 , a negative regulator of mTORC1 , caused activation of mTORC1 and enhanced Cd induction of the IRE1-JNK pathway and apoptosis without affecting other UPR branches
Ramírez-Rangel et al., Mol Cell Biol 2011 : GRp58/ERp57 knockdown reduces mTORC1 levels and phosphorylation of 4E-BP1 and p70 ( S6K ) in response to insulin ... In contrast, GRp58/ERp57 overexpression increases mTORC1 levels and activity ... In contrast, GRp58/ERp57 overexpression increases mTORC1 levels and activity
Grosso et al., PloS one 2011 : In spite of this, mTORc1 inhibition reduces eIF4F complex formation, and depresses translocation of TOP mRNAs on polysomes
Pang et al., World J Gastroenterol 2013 : Furthermore, TM treatment also activated mTORC1 , and in turn reduced Akt phosphorylation, which suggested the PI3K/Akt/mTOR signal pathway was involved in the TM-induced autophagic response in EC109 cells
Pollizzi et al., Molecular cancer 2009 (Disease Models, Animal...) : Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1 and suppression of AKT ... Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1 and suppression of AKT ... Recent studies indicate that inhibition of mTORC1 with RAD001 ( everolimus ) leads to rebound activation of AKT , which could protect tumors from drug induced cell death
Lu et al., Blood 2013 (Multiple Myeloma) : We identify TSC2 , a negative regulator of mTOR-C1 , as a novel Pim2 substrate and show that Pim2 directly phosphorylates TSC2 on Ser-1798 and relieves the suppression of TSC2 on mTOR-C1
Sciarretta et al., Circulation 2012 (Metabolic Syndrome X...) : Rheb inhibition causes mTORC1 inhibition, because forced activation of Rheb, through Rheb overexpression in vitro and through inducible cardiac-specific Rheb overexpression in vivo, restored mTORC1 activity ... Restoration of autophagy, through Atg7 reexpression and inhibition of mTORC1 , increased cellular ATP content and reduced endoplasmic reticulum stress, thereby reducing CM death induced by Rheb activation
Real et al., PloS one 2011 : The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1 's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process ... The effect of E2F1 on the activation of mTORC1 does not depend on Akt ... Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine
Kladney et al., Cancer Res 2010 (Prostatic Intraepithelial Neoplasia...) : Here, we engineered constitutive mTORC1 activation in prostate epithelium by a conditional genetic deletion of tuberous sclerosis complex 1 (Tsc1) , a potent negative regulator of mTORC1 signaling
Shortt et al., Blood 2013 (Lymphoma, B-Cell) : Moreover, apoptosis was initiated at drug concentrations insufficient to antagonize PI3K/mTORC2 regulated AKT phosphorylation
Vadlakonda et al., Frontiers in oncology 2013 : We present in this article, a hypothesis that activation of Akt-T308 phosphorylation in the presence of high ATP : AMP ratio promotes the stability of its phosphorylations and activates mTORC1 and the energy consuming biosynthetic processes
Lee et al., PloS one 2010 (Endotoxemia) : Furthermore, in vitro cellular studies demonstrated that LPS ( lipopolysaccharide ) activation of mTORC1-S6K still occurs in the presence of PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways ... Furthermore, in vitro cellular studies demonstrated that LPS ( lipopolysaccharide ) activation of mTORC1-S6K still occurs in the presence of PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways ... Furthermore, in vitro cellular studies demonstrated that LPS ( lipopolysaccharide ) activation of mTORC1-S6K still occurs in the presence of PI3K-Akt inhibition alone, but can be suppressed by concurrent inhibition of PI3K-Akt and MEK-ERK pathways
Patel et al., J Oral Pathol Med 2013 (Carcinoma, Squamous Cell...) : Indeed, inhibition of OCT-3 expression and activity in HNSCC cells prevented metformin induced AMP activated protein kinase activation and mTORC1 pathway inhibition
Yu et al., Cancer Res 2010 (Neoplasms) : Importantly, consistent with genetic ablation of mTORC2, WYE-132 targeted P-AKT ( S473 ) and AKT function without significantly reducing the steady-state level of the PI3K/PDK1 activity biomarker P-AKT ( T308 ), highlighting a prominent and direct regulation of AKT by mTORC2 in cancer cells
Elmasri et al., Angiogenesis 2012 : FABP4 was strongly regulated by mTORC1 and inhibited by Rapamycin
Tzatsos et al., J Biol Chem 2007 : Energy depletion activates AMP activated protein kinase (AMPK) and inhibits cell growth via TSC2 dependent suppression of mTORC1 signaling
Sini et al., Autophagy 2010 (Neoplasms) : mTORC1 activates p70S6K , which in turn phosphorylates the ribosomal protein S6 and 4E-BP1, both involved in protein translation ... mTORC2 activates AKT directly by phosphorylating Serine 473
Zhao et al., Neoplasia (New York, N.Y.) 2012 (Neoplasms) : Recently, we and others found that DEPTOR , a naturally occurring inhibitor of both mTORC1 and mTORC2 , was degraded by SCF ( Skp1-Cullin-F box proteins ) E3 ubiquitin ligase, the founding member of cullin-RING-ligases ( CRLs ), resulting in mTOR activation and cell proliferation ... Recently, we and others found that DEPTOR , a naturally occurring inhibitor of both mTORC1 and mTORC2, was degraded by SCF ( Skp1-Cullin-F box proteins ) E3 ubiquitin ligase, the founding member of cullin-RING-ligases ( CRLs ), resulting in mTOR activation and cell proliferation
Kamimura et al., Curr Biol 2008 : Here, we outline a PIP ( 3 ) -independent pathway linking temporal and spatial activation of PKBs by Tor complex 2 (TorC2) to the chemotactic response
Ai et al., J Clin Invest 2012 (Hyperinsulinism...) : Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice ... Pcsk9 is regulated by the transcription factor HNF1a, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCd, reduced activity of HNF4a and HNF1a, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels
Cao et al., Science signaling 2009 : Overall, this study suggests that Galpha ( i1 ) and Galpha ( i3 ) lie downstream of EGFR, but upstream of Gab1 mediated activation of Akt and mTORC1 , thus revealing a role for Galpha ( i ) proteins in mediating EGFR signaling
Pan et al., J Immunol 2013 : Its deficiency in DCs results in increased mammalian target of rapamycin (mTOR) complex 1 but decreased mTORC2 signaling, altered cytokine production, impaired CIITA/MHC-II expression, and defective Ag presentation to CD4 T cells after TLR4 stimulation
Melnik et al., Exp Dermatol 2013 : This hypothesis postulates that antiacne agents either enhance nuclear FoxO activity or inhibit mTORC1 ... Suppression of TNFa signalling by tetracyclines, erythromycin and other macrolides may attenuate IKKß-TSC1 mediated mTORC1 activation ... Antiandrogens may attenuate mTORC1 by suppressing mTORC2 mediated Akt/TSC2 signalling ... Antiandrogens may attenuate mTORC1 by suppressing mTORC2 mediated Akt/TSC2 signalling
Dunlop et al., Autophagy 2011 : ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding ... ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding ... Interestingly, ULK1 overexpression also increases phosphorylation of Raptor Ser863 and the mTOR autophosphorylation site, Ser2481 in a mTORC1 dependent manner ... Interestingly, ULK1 overexpression also increases phosphorylation of Raptor Ser863 and the mTOR autophosphorylation site, Ser2481 in a mTORC1 dependent manner ... Despite this evidence for heightened mTORC1 kinase activity following ULK1 overexpresssion, mTORC1 mediated phosphorylation of S6K1 and 4E-BP1 is significantly inhibited ... Despite this evidence for heightened mTORC1 kinase activity following ULK1 overexpresssion, mTORC1 mediated phosphorylation of S6K1 and 4E-BP1 is significantly inhibited ... We propose a new mechanism whereby ULK1 contributes to mTORC1 inhibition through hindrance of substrate docking to Raptor
Harwood et al., J Biol Chem 2008 (MAP Kinase Signaling System) : mTORC1 signaling can regulate growth factor activation of p44/42 mitogen activated protein kinases through protein phosphatase 2A ... mTORC1 signaling can regulate growth factor activation of p44/42 mitogen activated protein kinases through protein phosphatase 2A ... However, a role for mTORC1 signaling in modulating activation of p44/42 has not been reported ... However, a role for mTORC1 signaling in modulating activation of p44/42 has not been reported
Zheng et al., Nat Cell Biol 2011 : Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide binding ability of Rheb and inhibits Rheb mediated mTORC1 activation
Karni et al., Proc Natl Acad Sci U S A 2008 : mTORC1 activation by SF2/ASF bypasses upstream PI3K/Akt signaling and is essential for SF2/ASF mediated transformation, as inhibition of mTOR by rapamycin blocked transformation by SF2/ASF in vitro and in vivo
Yan et al., Mol Cell 2010 : We identify a transautophosphorylation site in the MAP4K3 kinase activation segment ( Ser170 ) that is required for MAP4K3 activity and its activation of mTORC1 signaling ... We propose that during amino acid sufficiency Ser170 phosphorylated MAP4K3 activates mTORC1 , but that upon amino acid restriction MAP4K3 preferentially interacts with PP2A ( T61 epsilon ), promoting dephosphorylation of Ser170, MAP4K3 inhibition, and, subsequently, inhibition of mTORC1 signaling
Rahimi et al., Cancer Res 2009 : mTORC2 promotes TGF-beta induced morphologic transformation and is required for TGF-beta induced Akt S473 phosphorylation but not mTORC1 activation
Pistollato et al., PloS one 2009 (Brain Neoplasms...) : Here, we investigate the role of mTOR signaling in the regulation of HIF-1alpha stability in primary GBM derived cells maintained under hypoxia ( 2 % oxygen )
Origanti et al., Biochem J 2012 (Cell Transformation, Neoplastic) : Inhibition of mTORC1 also reduced the association of the mRNA binding protein HuR with the ODC transcript
Yang et al., Cell cycle (Georgetown, Tex.) 2010 (Neoplasms) : Akt activity is well-known regulated through its phosphorylation at T308 and S473 by PDK1 and mTOrC2 , respectively
Floc'h et al., Cancer Res 2012 (Disease Models, Animal...) : In human prostate cancer cell lines, although not in the mouse model, the synergistic actions of MK-2206 and ridaforolimus ( MK-8669 ) are due in part to limiting the mTORC2 feedback activation of Akt
Ji et al., Oncogene 2010 (Neoplasms) : Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin induced apoptosis by promoting AMPK activation and mTORC1 inhibition
Fortress et al., Learn Mem 2013 (MAP Kinase Signaling System) : Here, we asked whether the enhancement of object recognition memory consolidation produced by dorsal hippocampal infusion of 17ß-estradiol ( E ( 2 ) ) is dependent on mTOR signaling in the dorsal hippocampus, and whether E ( 2 ) -induced mTOR signaling is dependent on dorsal hippocampal phosphatidylinositol 3-kinase (PI3K) and extracellular signal regulated kinase ( ERK ) activation
Shen et al., International journal of clinical and experimental pathology 2010 (Carcinoma, Endometrioid...) : mTORC1 and mTORC2 phosphorylatively regulate their respective downstream effectors p70S6K/4EBP1 , and Akt ... mTORC1 and mTORC2 phosphorylatively regulate their respective downstream effectors p70S6K/4EBP1 , and Akt ... mTORC1 and mTORC2 phosphorylatively regulate their respective downstream effectors p70S6K/4EBP1 , and Akt ... mTORC1 and mTORC2 phosphorylatively regulate their respective downstream effectors p70S6K/4EBP1 , and Akt ... mTORC1 and mTORC2 phosphorylatively regulate their respective downstream effectors p70S6K/4EBP1 , and Akt ... mTORC1 and mTORC2 phosphorylatively regulate their respective downstream effectors p70S6K/4EBP1 , and Akt
Phu et al., Cell Signal 2011 : Overexpressed DLK induced the phosphorylation of TORC2 and TORC1 on Ser-171 and 167, respectively and on additional residues
Vojtechová et al., Neoplasia (New York, N.Y.) 2008 : Regulation of mTORC1 signaling by Src kinase activity is Akt1 independent in RSV transformed cells
Han et al., Clin Cancer Res 2009 (Chordoma) : Strikingly, expression of PTEN , a negative regulator of mTORC1 signaling, was not detected or significantly reduced in chordoma derived cell lines and primary tumors
Tanwar et al., PLoS Genet 2012 (Adenoma...) : Deletion of the genes for Tuberous Sclerosis 1 (Tsc1) or Tsc2, regulators of mTORC1 that are downstream of LKB1 signaling, in the oviductal and uterine stroma phenocopies some of the defects observed in Lkb1 mutant mice, confirming that dysregulated mTORC1 activation in the Lkb1 deleted stroma contributes to the phenotype ... Deletion of the genes for Tuberous Sclerosis 1 (Tsc1) or Tsc2 , regulators of mTORC1 that are downstream of LKB1 signaling, in the oviductal and uterine stroma phenocopies some of the defects observed in Lkb1 mutant mice, confirming that dysregulated mTORC1 activation in the Lkb1 deleted stroma contributes to the phenotype ... Loss of PTEN , an upstream regulator of mTORC1 signaling, along with Lkb1 deletion significantly increased tumor burden in uteri and induced tumorigenesis in the cervix and vagina
Willems et al., Leukemia 2012 (Leukemia, Myeloid, Acute) : In addition, the mTORC1 dependent PI3K/Akt feedback activation was fully abrogated in AZD8055 treated AML cells ... In addition, the mTORC1 dependent PI3K/Akt feedback activation was fully abrogated in AZD8055 treated AML cells
Zhang et al., Free Radic Biol Med 2009 : In this study we report the effect of H ( 2 ) O ( 2 ) on insulin stimulated mTORC1 activity and assembly using A549 and bovine aortic smooth muscle cells ... These findings are consistent with PRAS40 functioning as a negative regulator of insulin stimulated mTORC1 activity during oxidant stress
Jaba et al., J Clin Invest 2013 : NOS inhibitor L-NAME also significantly attenuated RGS4 degradation, and reduced activation of AKT/mTORC1 signaling and induction of myocardial hypertrophy in PlGF transgenic mice, while conditional cardiac-specific PlGF expression in eNOS knockout mice did not induce myocardial hypertrophy
Stevens et al., J Biol Chem 2009 : Peptide combinatorial libraries identify TSC2 as a death associated protein kinase ( DAPK ) death domain binding protein and reveal a stimulatory role for DAPK in mTORC1 signaling ... DAPK ( +/- ) mouse embryo fibroblasts have attenuated mTORC1 signaling compared with DAPK+/+ counterparts, and overexpression of DAPK in DAPK ( +/- ) MEFs stimulates mTORC1 activity ... DAPK ( +/- ) mouse embryo fibroblasts have attenuated mTORC1 signaling compared with DAPK+/+ counterparts, and overexpression of DAPK in DAPK ( +/- ) MEFs stimulates mTORC1 activity
Li et al., Cell Signal 2010 : These data suggest that PP2A and AMPK mediated phosphorylation of Raptor mediate H ( 2 ) O ( 2 ) -induced inhibition of mTORC1 signaling
Jaafar et al., J Biol Chem 2011 : Vasopressin stimulation also induced phosphorylation of Akt on Ser-473 through PLD1 dependent activation of mTORC2 complex
Lorne et al., Am J Respir Cell Mol Biol 2009 (Acute Lung Injury) : Rapamycin pretreatment inhibited PAM- or LPS induced mTORC1 activation in the lungs
Kumar et al., Mol Cell Biol 2008 : Since little is known about the role of either rictor or mTORC2 in PI-3 kinase mediated physiological processes in adult animals, we generated muscle-specific rictor knockout mice
O'Brien et al., Arch Immunol Ther Exp (Warsz) 2012 (MAP Kinase Signaling System) : Furthermore, we highlight the importance of tight control of mTOR signaling by tuberous sclerosis complex 1 for T-cell homeostasis, and the regulation of mTOR signaling by diacylglycerol kinases and the RasGRP1-Ras-Erk1/2 pathway in the context of TCR signaling ... Furthermore, we highlight the importance of tight control of mTOR signaling by tuberous sclerosis complex 1 for T-cell homeostasis, and the regulation of mTOR signaling by diacylglycerol kinases and the RasGRP1-Ras-Erk1/2 pathway in the context of TCR signaling ... Furthermore, we highlight the importance of tight control of mTOR signaling by tuberous sclerosis complex 1 for T-cell homeostasis, and the regulation of mTOR signaling by diacylglycerol kinases and the RasGRP1-Ras-Erk1/2 pathway in the context of TCR signaling
Sato et al., J Biol Chem 2009 : The activation of mTORC1 by Rheb can be faithfully reproduced in vitro by using mTORC1 immunoprecipitated by the use of anti-raptor antibody from mammalian cells starved for nutrients ... Both Rheb1 and Rheb2 activate mTORC1 ... Both Rheb1 and Rheb2 activate mTORC1 ... FKBP38, a recently proposed mediator of Rheb action, appears not to be involved in the Rheb dependent activation of mTORC1 in vitro, because the preparation of mTORC1 that is devoid of FKBP38 is still activated by Rheb ... PRAS40, a TOR signaling ( TOS ) motif containing protein that competes with the binding of 4EBP1 to mTORC1, inhibits Rheb induced activation of mTORC1
Wolin , Cancer Lett 2013 (Neuroendocrine Tumors...) : The mTOR inhibitor everolimus has been approved by the FDA for the treatment of pNET, but its efficacy may be limited by its inability to prevent mTORC2 mediated activation of Akt
Finlay , Biochem Soc Trans 2013 : mTORC1 regulates glucose metabolism in CTLs through regulating the expression of the transcription factor HIF1a ( hypoxia-inducible factor 1a )
Marzec et al., PloS one 2011 (Lymphoma, T-Cell, Cutaneous) : mTORC1 activates p70S6kinase 1 (p70S6K1) and inhibits 4E-binding protein 1 (4E-BP1) ... mTORC1 activates p70S6kinase 1 (p70S6K1) and inhibits 4E-binding protein 1 (4E-BP1)
Audhya et al., EMBO J 2004 : Consistent with these findings, phosphorylation of Slm1 and Slm2 was dependent on TORC2 protein kinase activity, both in vivo and in vitro, and Slm1 localization required both PI4,5P ( 2 ) and functional TORC2 ... Consistent with these findings, phosphorylation of Slm1 and Slm2 was dependent on TORC2 protein kinase activity, both in vivo and in vitro, and Slm1 localization required both PI4,5P ( 2 ) and functional TORC2
Kato et al., Cell Death Differ 2012 (MAP Kinase Signaling System) : Activation of mTORC1 reduced Akt phosphorylation, which was an event upstream of IRE-JNK signaling and consequent apoptosis ... These results disclosed that, under ER stress conditions, mTORC1 causes apoptosis through suppression of Akt and consequent induction of the IRE1-JNK pathway
Wagner et al., Am J Physiol Cell Physiol 2010 : Rheb overexpression induced mTORC1 activity and repressed contractile protein expression, but a farnesylation-deficient mutant ( C18S ) elicited the opposite effect ... Notably, mTORC1 activity was elevated in VSMC isolated from an intimal hyperplastic patient lesion compared with normal media, and lovastatin treatment inhibited mTORC1 activity in these cultures
Cam et al., Mol Cell 2010 : mTORC1 signaling under hypoxic conditions is controlled by ATM dependent phosphorylation of HIF-1a
Ohmae et al., J Biol Chem 2006 : Although these were previously shown to activate Ca ( 2+ ) /cAMP-response element binding protein ( CREB ) -dependent transcription, we here show that CL1 and CL2 were unable to significantly phosphorylate CREB Ser-133 and rather inhibited CRE dependent gene expression by a dominant mechanism that bypassed CREB and was mediated by phosphorylated TORC2
Magee et al., Cell stem cell 2012 (Leukemia) : Pten is therefore required in adult, but not neonatal, HSCs to negatively regulate mTORC2 signaling
Lee et al., Oncogene 2012 (Carcinoma, Non-Small-Cell Lung...) : This demonstrates that the pro-oncogenic activity of TR3 in lung cancer cells was due to inhibition of p53 and activation of mTORC1
Koh et al., Endocr Relat Cancer 2012 (Carcinoma...) : Cells treated with everolimus demonstrated activation of Akt and Ret via TORC2 complex dependent and TORC2 complex independent mechanisms respectively ... Cells treated with everolimus demonstrated activation of Akt and Ret via TORC2 complex dependent and TORC2 complex independent mechanisms respectively
Vega-Rubin-de-Celis et al., Biochemistry 2010 : REDD1 is induced by hypoxia, and REDD1 overexpression is sufficient to inhibit mTORC1 ... mTORC1 is regulated by the small GTPase Rheb , which in turn is regulated by the GTPase activating protein complex, TSC1/TSC2 ... REDD1 induced-mTORC1 inhibition requires the TSC1/TSC2 complex , and REDD1 has been proposed to act by directly binding to and sequestering 14-3-3 proteins away from TSC2 leading to TSC2 dependent inhibition of mTORC1 ... REDD1 induced-mTORC1 inhibition requires the TSC1/TSC2 complex, and REDD1 has been proposed to act by directly binding to and sequestering 14-3-3 proteins away from TSC2 leading to TSC2 dependent inhibition of mTORC1 ... REDD1 induced-mTORC1 inhibition requires the TSC1/TSC2 complex, and REDD1 has been proposed to act by directly binding to and sequestering 14-3-3 proteins away from TSC2 leading to TSC2 dependent inhibition of mTORC1 ... Sequence conservation mapping to the surface of the structure and mutagenesis studies demarcated a hotspot likely to interact with effector proteins that is essential for REDD1 mediated mTORC1 inhibition
Laplante et al., Cell Metab 2012 (Obesity) : DEPTOR activates the proadipogenic Akt/PKB-PPAR-? axis by dampening mTORC1 mediated feedback inhibition of insulin signaling
Dennis et al., J Biol Chem 2011 : Mechanisms involved in the coordinate regulation of mTORC1 by insulin and amino acids ... In this study, we explored the coordinate regulation of mTORC1 by insulin and amino acids ... In deprived cells, mTORC1 was activated by expressing either constitutively active ( ca ) Rheb or a caRagB·caRagC complex, and coexpression of the constructs had an additive effect
Wang et al., J Biol Chem 2009 : Inhibition of mTORC1 or mTORC2 by transiently or moderately activated MEK/ERK caused moderately enhanced Beclin 1 resulting in cytoprotective autophagy, whereas inhibition of both mTORC1 and mTORC2 by sustained MEK/ERK activation caused strongly pronounced Beclin 1 leading to cytodestructive autophagy ... Inhibition of mTORC1 or mTORC2 by transiently or moderately activated MEK/ERK caused moderately enhanced Beclin 1 resulting in cytoprotective autophagy, whereas inhibition of both mTORC1 and mTORC2 by sustained MEK/ERK activation caused strongly pronounced Beclin 1 leading to cytodestructive autophagy ... Inhibition of mTORC1 or mTORC2 by transiently or moderately activated MEK/ERK caused moderately enhanced Beclin 1 resulting in cytoprotective autophagy, whereas inhibition of both mTORC1 and mTORC2 by sustained MEK/ERK activation caused strongly pronounced Beclin 1 leading to cytodestructive autophagy
Lyo et al., Biochem Biophys Res Commun 2010 (Kidney Neoplasms) : We report here that the PLD/mTOR dependent stabilization of HDM2 involves mTORC2 and the AGC family kinase serum- and glucocorticoid-inducible kinase 1 ( SGK1 )
Lishner et al., Cell Signal 2008 (Multiple Myeloma) : Herein we demonstrate that the anti-myeloma effect of CD81/CD82 involves a down-regulation of Akt, activation of FoxO transcription factors and a decrease in active mTOR and mTOR/rictor ... Herein we demonstrate that the anti-myeloma effect of CD81/CD82 involves a down-regulation of Akt, activation of FoxO transcription factors and a decrease in active mTOR and mTOR/rictor
Kim et al., J Biol Chem 2010 (Breast Neoplasms...) : In contrast, API-1 had no effects on the activities of the upstream Akt activators, phosphatidylinositol 3-kinase, phosphatidylinositol dependent kinase-1, and mTORC2
Zeng et al., Nature 2013 (Inflammation) : By contrast, mTORC1 does not directly affect the expression of Foxp3 or anti- and pro-inflammatory cytokines in T ( reg ) cells, suggesting a non-conventional mechanism for T ( reg ) -cell functional regulation
Saci et al., Mol Cell 2011 : Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size ... Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size
Zha et al., Cancer Lett 2011 (Cell Transformation, Neoplastic) : Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor , in this process
Ekim et al., Mol Cell Biol 2011 : mTOR kinase domain phosphorylation promotes mTORC1 signaling, cell growth, and cell cycle progression
Wang et al., J Biol Chem 2009 : Raptor ( regulatory associated protein of mammalian target of rapamycin (mTOR) ), a constitutively binding protein of mTORC1, is essential for mTORC1 activity and critical for the regulation of mTORC1 activity in response to insulin signaling and nutrient and energy sufficiency ... Raptor ( regulatory associated protein of mammalian target of rapamycin (mTOR) ), a constitutively binding protein of mTORC1, is essential for mTORC1 activity and critical for the regulation of mTORC1 activity in response to insulin signaling and nutrient and energy sufficiency
Fang et al., J Biol Chem 2012 (Prostatic Neoplasms) : Significantly, androgen increased TORC2 mediated AKT S473 phosphorylation without affecting the PDK1 mediated AKT T308 phosphorylation or TORC1 activity ... This study reveals a pathway linking AR to a selective activation of TORC2 , the subsequent activation of AKT , and phosphorylation of a discrete set of AKT substrates that regulate cellular proliferation and survival
Yoon et al., J Cell Sci 2008 : Instead, PLD1 positively regulates mTOR signaling leading to the production of IGF2, an autocrine factor instrumental for the initiation of satellite cell differentiation ... Instead, PLD1 positively regulates mTOR signaling leading to the production of IGF2, an autocrine factor instrumental for the initiation of satellite cell differentiation
Bentzinger et al., Cell Metab 2008 (Muscular Dystrophies) : Finally, we show that activation of PKB/Akt does not require mTORC2 ... Finally, we show that activation of PKB/Akt does not require mTORC2
Chakrabarti et al., Mol Endocrinol 2008 : The activity of mTORC1 in 3T3-L1 adipocytes was up-regulated by stable expression of either constitutively active Rheb or dominant negative AMP activated protein kinase
Yuan et al., CNS Neurosci Ther 2012 (Glioblastoma) : Subsequently, activated AMPK inhibited mTOR signaling and downregulated antiapoptosis protein Bcl-2, which was contributed to the additive antiproliferation effects of combination treatment
Vadysirisack et al., Mol Cell Biol 2011 : We show that Redd1 loss leads to elevated mammalian TORC1 (mTORC1) activity, which explains the increased p53 translation and protein levels ... Together, these findings suggest that REDD1 mediated suppression of mTORC1 activity exerts feedback control on p53, thereby limiting the apoptotic response and contributing to cellular survival following DNA damage
Zou et al., Dev Cell 2011 : Rheb1 is required for mTORC1 and myelination in postnatal brain development ... Our study demonstrates that Rheb1 is essential for mTORC1 signaling and myelination in the brain, and suggests that mTORC1 signaling plays a role in selective cellular adaptations, rather than general cellular viability
Shao et al., J Hepatol 2012 (Carcinoma, Hepatocellular...) : The inhibition of both mTORC1/2 not only efficiently blocked mTORC1 signaling, but also abrogated AKT-feedback activation caused by selective mTORC1 inhibition
Fonseca et al., J Biol Chem 2011 : Our data also reveal striking diversity in the requirements for MEK/ERK in the control of mTORC1 between different cell types, pointing to additional signaling connections between phorbol esters and mTORC1, which do not involve MEK/ERK
Chen et al., Dev Cell 2010 : Activated FoxO1 inhibits mTORC1 by TSC2 dependent and TSC2 independent mechanisms ... Sesn3 , in turn, inhibits mTORC1 activity in Tsc2-proficient cells ... Thus, under stress conditions, FoxO inhibits the anabolic activity of mTORC1 , a major consumer of cellular energy, while activating Akt, which increases cellular energy metabolism, thereby maintaining cellular energy homeostasis
Bakan et al., Curr Opin Lipidol 2012 : Recent studies indicate that mTORC1 regulates SREBP-1 activation at multiple levels
Chao et al., J Agric Food Chem 2011 (Glioblastoma) : Activation of AMPK induces a-mangostin mediated phosphorylation of raptor, which subsequently associates with 14-3-3? and results in the loss of mTORC1 activity
Ghosh et al., PloS one 2010 : Here we investigated the potential regulation of mTOR signaling by SIRT1 in response to nutrients and cellular stress ... We demonstrate that SIRT1 deficiency results in elevated mTOR signaling , which is not abolished by stress conditions ... Furthermore, we demonstrate that SIRT1 interacts with TSC2, a component of the mTOR inhibitory-complex upstream to mTORC1, and regulates mTOR signaling in a TSC2 dependent manner
Kuraishy et al., Proc Natl Acad Sci U S A 2007 (Cell Transformation, Neoplastic) : Here we show that the CREB coactivator TORC2 directly regulates TCL1 expression independent of CREB Ser-133 phosphorylation and CBP/p300 recruitment
Lu et al., Cancer Res 2010 (Skin Neoplasms) : Small GTPase Ras homologue enriched in brain (RHEB) binds and activates the key metabolic regulator mTORC1 , which has an important role in cancer cells, but the role of RHEB in cancer pathogenesis has not been shown
Blancquaert et al., Mol Endocrinol 2010 : mTORC1 dependent S6K1 phosphorylation in response to both insulin and cAMP required amino acids, whereas inhibition of AMP activated protein kinase and glycogen synthase kinase 3 enhanced insulin but not cAMP effects
Huang et al., Mol Cell Biol 2008 : However, how mTORC2 is regulated and whether the TSC1-TSC2 complex is involved are unknown ... Our data also suggest that the TSC1-TSC2 complex positively regulates mTORC2 in a manner independent of its GTPase activating protein activity toward Rheb ... These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2, which through different mechanisms promotes Akt activation ... These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2 , which through different mechanisms promotes Akt activation
McKinney et al., Genes Dev 2013 (Cytomegalovirus Infections) : Coordinate control of PABP1, Paip2, and EDD1 required the virus encoded UL38 mTORC1 activator and resulted in augmented Paip2 synthesis, stability, and association with PABP1 ... Coordinate control of PABP1, Paip2 , and EDD1 required the virus encoded UL38 mTORC1 activator and resulted in augmented Paip2 synthesis, stability, and association with PABP1 ... Coordinate control of PABP1 , Paip2, and EDD1 required the virus encoded UL38 mTORC1 activator and resulted in augmented Paip2 synthesis, stability, and association with PABP1
Foster et al., J Biol Chem 2010 (MAP Kinase Signaling System) : These data suggest that mTORC1 activation leads to raptor multisite phosphorylation and that raptor Ser ( 863 ) phosphorylation functions as a master biochemical switch that modulates hierarchical raptor phosphorylation ( e.g. on Ser ( 859 ) and Ser ( 855 ) )
Yuan et al., J Biol Chem 2012 (Insulin Resistance) : Lrictor ( KO ) mice also manifest defects in insulin activated mTORC1 activity, evidenced by decreased S6 kinase and Lipin1 phosphorylation
Tan et al., Cancer Cell 2010 (Cell Transformation, Neoplastic...) : On loss of PPP2R2B, mTORC1 inhibitor rapamycin triggers a compensatory Myc phosphorylation in PDK1 dependent, but PI3K and AKT independent manner, resulting in resistance ... On loss of PPP2R2B, mTORC1 inhibitor rapamycin triggers a compensatory Myc phosphorylation in PDK1 dependent, but PI3K and AKT independent manner, resulting in resistance
Guertin et al., Dev Cell 2006 : Thus, mTORC1 function is essential in early development, mLST8 is required only for mTORC2 signaling, and mTORC2 is a necessary component of the Akt-FOXO and PKCalpha pathways
Finlay et al., J Exp Med 2012 : The present study now demonstrates that mTORC1 activity in CD8 ( + ) T cells is not dependent on PI3K or Akt but is critical to sustain glucose uptake and glycolysis in CD8 ( + ) T cells ... The present study now demonstrates that mTORC1 activity in CD8 ( + ) T cells is not dependent on PI3K or Akt but is critical to sustain glucose uptake and glycolysis in CD8 ( + ) T cells
Hiraoka et al., Oncogene 2011 : A well conserved threonine in the turn motif ( TM ) is also constitutively phosphorylated by mTORC2 and contributes to the stability of Akt
Mazei-Robison et al., Neuron 2011 : Chronic morphine decreases mTORC2 activity, and overexpression of Rictor , a component of mTORC2, prevents morphine induced changes in cell morphology and activity
Wang et al., J Biol Chem 2006 : Here we demonstrate that insulin produces a stable increase in the kinase activity of mTORC1 in 3T3-L1 adipocytes ... The stimulatory effects of insulin on both 4EBP1 kinase activity and binding occurred rapidly and at physiological concentrations of insulin, and both effects required an intact mTORC1 ... The stimulatory effects of insulin on both 4EBP1 kinase activity and binding occurred rapidly and at physiological concentrations of insulin, and both effects required an intact mTORC1
Mills et al., Proc Natl Acad Sci U S A 2008 (Lymphoma) : Here, we demonstrate that loss of TSC2 in the E mu-myc murine lymphoma model leads to mTORC1 activation and accelerated oncogenesis caused by a defective apoptotic program despite compromised AKT phosphorylation
Yip et al., Mol Cell 2010 : Extended incubation with FKBP12-rapamycin compromises the structural integrity of mTORC1 in a stepwise manner, leading us to propose a model in which rapamycin inhibits mTORC1 mediated phosphorylation of 4E-BP1 and S6K1 through different mechanisms ... Extended incubation with FKBP12-rapamycin compromises the structural integrity of mTORC1 in a stepwise manner, leading us to propose a model in which rapamycin inhibits mTORC1 mediated phosphorylation of 4E-BP1 and S6K1 through different mechanisms
Weston et al., J Neurosci 2012 (Synaptic Transmission) : We therefore performed an electrophysiological and morphological comparison of glutamatergic and GABAergic neurons in which mTOR signaling was either increased by loss of the repressor Pten or decreased by treatment with rapamycin
Sviripa et al., Bioorg Med Chem Lett 2013 : AMPK also regulates lipid synthesis by inhibiting acetyl-CoA carboxylase (ACC) and regulates mTOR signaling by activating TSC2 ... AMPK also regulates lipid synthesis by inhibiting acetyl-CoA carboxylase (ACC) and regulates mTOR signaling by activating TSC2 ... AMPK also regulates lipid synthesis by inhibiting acetyl-CoA carboxylase (ACC) and regulates mTOR signaling by activating TSC2
Orlova et al., J Clin Invest 2010 : STRADalpha deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice ... Consistent with the observations in human PMSE brain, knockdown of STRADalpha in vivo resulted in cortical malformation, enhanced mTORC1 activation , and abnormal nuclear localization of LKB1
Shaw , Acta Physiol (Oxf) 2009 (Neoplasms) : Many details of the molecular mechanism by which AMPK inhibits mTORC1 signalling have also been decoded in the past 5 years
Dentin et al., Nature 2007 (Diabetes Mellitus) : Insulin disrupts TORC2 activity by induction of the Ser/Thr kinase SIK2, which we show here undergoes AKT2 mediated phosphorylation at Ser 358 ... Activated SIK2 in turn stimulated the Ser 171 phosphorylation and cytoplasmic translocation of TORC2
Hussain et al., Mol Cell Biol 2013 : Here, we show that the ubiquitin hydrolase UCH-L1 regulates the balance of mTOR signaling by disrupting mTORC1
Gupta et al., Blood 2012 (Lymphoma) : Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma dependent apoptosis in lymphoid malignancies ... Dual mTORC1/mTORC2 inhibition diminishes Akt activation and induces Puma dependent apoptosis in lymphoid malignancies
Xu et al., J Biol Chem 2012 : Recent work has implicated a role for cullin-RING E3 ubiquitin ligase 7 ( CRL7 ) in targeting IRS1 for mTORC1/S6K1 dependent degradation
Fumarola et al., Breast Cancer Res Treat 2013 (Breast Neoplasms) : The key role of AMPK dependent inhibition of mTORC1 in sorafenib mechanisms of action was confirmed by AMPKa1 silencing, which restored mTORC1 activity conferring a significant protection from cell death
Wang et al., Mol Cell Biol 2012 (Dermatitis, Seborrheic) : Surprisingly, however, TORC2 does not regulate cell growth via its best characterized target, AKT
Dunlop et al., Cell Signal 2009 : Finally, we show that activation of mTORC1 by both Rheb and RhebL1 is impaired by FKBP38 ... Finally, we show that activation of mTORC1 by both Rheb and RhebL1 is impaired by FKBP38 ... Finally, we show that activation of mTORC1 by both Rheb and RhebL1 is impaired by FKBP38
Rapley et al., J Biol Chem 2011 : We examined the mechanism and contribution of this enhancement to insulin activation of mTORC1 signaling in 293E and HeLa cells ... Furthermore, Rheb overexpression in 293E activated mTORC1 signaling completely without causing PRAS40 release
Timmerman et al., Diabetes 2010 : This defect is associated with impaired insulin induced vasodilation and mTORC1 signaling
Cleveland-Donovan et al., Endocrinology 2010 (Obesity) : The mammalian target of rapamycin (mTOR)-Rictor complex regulates phosphorylation of AKT-serine ( 473 ) in 3T3-L1 adipocytes, but knockdown of Rictor by lentivirus delivered short hairpin RNA in sc preadipocytes did not affect AKT-serine ( 473 ) phosphorylation by IGF-I
Lazorchak et al., Mol Cell 2010 : We further show that Akt2 specifically mediates the Sin1-mTORC2 dependent suppression of il7r and rag gene expression in B cells by regulating FoxO1 phosphorylation
Magri et al., Cell stem cell 2011 (Epilepsy...) : Notably, mTORC1 dependent Akt inhibition and STAT3 activation were involved in the reduced self-renewal and earlier neuronal and astroglial differentiation of mutant NSCs ... Notably, mTORC1 dependent Akt inhibition and STAT3 activation were involved in the reduced self-renewal and earlier neuronal and astroglial differentiation of mutant NSCs
Chen et al., J Biol Chem 2011 : The PI3K dependent signaling kinase complex mTORC2 ( mammalian target of rapamycin complex 2 ) has been defined as the regulatory Ser-473 kinase of Akt
Wang et al., Circ Res 2007 (Coronary Artery Disease...) : We found that IFN-gamma mediated vascular smooth muscle cell proliferation and intimal expansion were associated with phosphorylation of the mTORC1 effector ribosomal protein S6 kinase 1, that the graft morphological changes and S6 kinase 1 activation were inhibited by the mTORC1 inhibitor rapamycin in vivo, and that IFN-gamma induced mTORC1 signaling was dependent on phosphatidylinositol 3-kinase activity under serum-free conditions in vitro
Masri et al., Cancer Res 2007 (Brain Neoplasms...) : mTORC2 has recently been shown to phosphorylate and activate Akt
Yang et al., Proc Natl Acad Sci U S A 2006 : We also observed that Rheb does not activate TORC2 in human embryonic kidney 293 cells, although it potently stimulates TORC1
Park et al., Haematologica 2010 (Leukemia, Myeloid, Acute) : However, as mTORC1 activation is independent of PI3K/AKT in acute myeloid leukemia, dual PI3K and mTOR inhibitors may induce apoptosis in blast cells ... However, as mTORC1 activation is independent of PI3K/AKT in acute myeloid leukemia, dual PI3K and mTOR inhibitors may induce apoptosis in blast cells ... However, as mTORC1 activation is independent of PI3K/AKT in acute myeloid leukemia, dual PI3K and mTOR inhibitors may induce apoptosis in blast cells
Tan et al., PloS one 2013 : In this study, we discovered that mTORC1 regulates REDD1 protein stability in a 26S proteasome dependent manner ... Inhibition of mTORC1 resulted in reduced REDD1 protein stability and a consequent decrease in REDD1 expression
Fetalvero et al., Mol Cell Biol 2013 (Myopathies, Structural, Congenital) : These results suggest that aberrant mTORC1 signaling and impaired autophagy are consequences of the loss of Mtm1 and may play a primary role in disease pathogenesis
Gundermann et al., J Appl Physiol 2012 (Hyperemia) : BFR exercise increased the phosphorylation of mTOR, S6 kinase 1, ribosomal protein S6 , ERK1/2, and Mnk1 interacting kinase 1 ( P < 0.05 ) with no changes in mTORC1 signaling in the SNP trial ( P > 0.05 ) ... BFR exercise increased the phosphorylation of mTOR, S6 kinase 1, ribosomal protein S6, ERK1/2 , and Mnk1 interacting kinase 1 ( P < 0.05 ) with no changes in mTORC1 signaling in the SNP trial ( P > 0.05 ) ... BFR exercise increased the phosphorylation of mTOR , S6 kinase 1, ribosomal protein S6, ERK1/2, and Mnk1 interacting kinase 1 ( P < 0.05 ) with no changes in mTORC1 signaling in the SNP trial ( P > 0.05 ) ... BFR exercise increased the phosphorylation of mTOR, S6 kinase 1, ribosomal protein S6, ERK1/2 , and Mnk1 interacting kinase 1 ( P < 0.05 ) with no changes in mTORC1 signaling in the SNP trial ( P > 0.05 )
Wolff et al., Mol Cell Biol 2011 (Anoxia) : Cell-type dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia ... We previously reported that mTORC1 regulation by hypoxia involves Redd1 and the Tsc1/Tsc2 complex ... We previously reported that mTORC1 regulation by hypoxia involves Redd1 and the Tsc1/Tsc2 complex ... AMPK activation ( using 5-aminoimidazole-4-carboxamide riboside [ AICAR ] ) induces raptor phosphorylation and inhibits mTORC1 in both mouse embryo fibroblasts ( MEFs ) and hepatocytes, but whereas mTORC1 inhibition is Tsc1/Tsc2 dependent in MEFs, it is independent in hepatocytes ... AMPK activation ( using 5-aminoimidazole-4-carboxamide riboside [ AICAR ] ) induces raptor phosphorylation and inhibits mTORC1 in both mouse embryo fibroblasts ( MEFs ) and hepatocytes, but whereas mTORC1 inhibition is Tsc1/Tsc2 dependent in MEFs, it is independent in hepatocytes
Wu et al., Am J Pathol 2013 (Cardiomegaly...) : Cardiomyocyte apoptosis was reduced and mTORC1 activity was suppressed in cardiomyocyte Rheb1-deletion mice, suggesting that Rheb1 regulates mTORC1 activation in myocardium ... This study indicates that Rheb1 is essential for mTORC1 activation in cardiomyocytes and suggests that targeting Rheb1-mTORC1 signaling, such as by As-IV treatment, may be an effective therapeutic method for treating patients with adverse cardiac remodeling after MI and hypertrophy
Chou et al., PloS one 2012 : Indeed mTORC1 inhibitor rapamycin prevented HSF1-S326 phosphorylation, suggesting that this complex is involved in HSF1 regulation in stress
Flinn et al., Mol Biol Cell 2010 : These data suggest that integrity of late endosomes is essential for amino acid- and insulin stimulated mTORC1 signaling and that blocking the early/late endosomal conversion prevents mTOR from interacting with Rheb in the late endosomal compartment
Balasubramanian et al., Cardiovasc Hematol Agents Med Chem 2009 (Cardiomegaly) : mTORC2 regulates the actin cytoskeleton in addition to activating Akt ( Protein kinase B ) for the subsequent removal of proapoptotic factors via the UPS for cell survival
Xu et al., J Biol Chem 2012 : Cycloheximide, a translation elongation inhibitor known to augment intracellular amino acid levels, prevented the effect of bafilomycin on amino acids levels and completely reversed its inhibition of EGF induced mTORC1 activation
Chang et al., Eur J Immunol 2012 : Sin1 deficiency blocks the mTORC2 dependent Akt phosphorylation in T cells during development and activation
Akcakanat et al., Biochem Biophys Res Commun 2007 : mTORC1 is rapamycin-sensitive, and results in phosphorylation of 4E-BP1 and S6K1 ... mTORC1 is rapamycin-sensitive, and results in phosphorylation of 4E-BP1 and S6K1
Gwinn et al., Mol Cell 2008 : AMPK phosphorylation of the TSC2 tumor suppressor contributes to suppression of mTORC1 ; however, TSC2-deficient cells remain responsive to energy stress ... The phosphorylation of raptor by AMPK is required for the inhibition of mTORC1 and cell-cycle arrest induced by energy stress
Ju et al., Cell Signal 2013 : We have previously demonstrated that syndecan 4 (S4) regulates the intracellular localization of mTORC2 , thus altering phosphorylation of Akt at serine473 ( Ser473 ), one of two critical phosphorylation sites essential for the full activation of Akt [1 ]
Marzec et al., Blood 2008 (Lymphoma, T-Cell, Cutaneous) : The mTORC1 , PI3K/Akt, and MEK/ERK pathways could also be activated by IL-2 in the primary leukemic, mitogen preactivated CTCL cells
Hietakangas et al., Genes Dev 2007 : Here we analyze the role of TORC2 mediated AKT phosphorylation in Drosophila
Jaafar et al., Cell communication and signaling : CCS 2013 (Muscular Atrophy) : These observations suggest that PLD1 acts through the activation of both mTORC1 and mTORC2 to induce positive trophic effects on muscle cells ... These observations suggest that PLD1 acts through the activation of both mTORC1 and mTORC2 to induce positive trophic effects on muscle cells
Kuehn et al., J Biol Chem 2011 : In mouse bone marrow derived mast cells, PGE ( 2 ) was found to induce activation of mTORC1 ( mTOR complexed to raptor ) as indicated by increased p70S6K and 4E-BP1 phosphorylation, and activation of mTORC2 ( mTOR complexed to rictor ), as indicated by increased phosphorylation of AKT at position Ser ( 473 ) ... In mouse bone marrow derived mast cells, PGE ( 2 ) was found to induce activation of mTORC1 ( mTOR complexed to raptor ) as indicated by increased p70S6K and 4E-BP1 phosphorylation, and activation of mTORC2 ( mTOR complexed to rictor ), as indicated by increased phosphorylation of AKT at position Ser ( 473 )
Kwan et al., PloS one 2013 (Uterine Cervical Neoplasms) : Besides, impaired mTOR signaling activity also reduced DVL3 expression
Guo et al., Arterioscler Thromb Vasc Biol 2011 : According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor dependent Akt activation, which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity ... According to Western blot analysis and immunoprecipitation results, rHDL promoted mTOR phosphorylation, mTOR-rictor complex formation, and mTOR-rictor dependent Akt activation , which were accompanied by increased nuclear translocation of human telomerase reverse transcriptase and enhanced nuclear telomerase activity
Zhou et al., Cell Res 2013 : Third, we examined the involvement of transcription factor EB (TFEB) and demonstrated that TFEB activation following mTORC1 suppression is necessary but not sufficient for lysosomal activation
Lam et al., PLoS Pathog 2012 (Tuberculosis) : We identify the human quinone oxidoreductase NQO1 as a nitazoxanide target and propose, based on experiments with cells expressing NQO1 or not, that NQO1 inhibition is partly responsible for mTORC1 inhibition and enhanced autophagy
Joha et al., Oncogene 2012 (Leukemia, Myelogenous, Chronic, BCR-ABL Positive) : Our findings provide new mechanistic insights into the role of mTORC2 in BCR-ABL ( + ) cells and indicate that regulation by GILZ may influence TKI sensitivity ... Our findings provide new mechanistic insights into the role of mTORC2 in BCR-ABL ( + ) cells and indicate that regulation by GILZ may influence TKI sensitivity
Falcon et al., Cancer Res 2011 (Neoplasms, Experimental...) : In this study, we examined the effects of mTORC1/2 dual inhibition on VEGF production, tumor angiogenesis, vascular regression, and vascular regrowth, and we compared the effects of dual inhibition to mTORC1 inhibition alone
Wu et al., J Biol Chem 2012 : Although expression of the Raptor T908A mutant did not affect the mTORC1 integrity, it markedly impaired the mTORC1 activation by insulin or by overexpression of the small GTP binding protein RheB under nutrient starvation ... Although expression of the Raptor T908A mutant did not affect the mTORC1 integrity, it markedly impaired the mTORC1 activation by insulin or by overexpression of the small GTP binding protein RheB under nutrient starvation ... Our findings demonstrate an important role for ICK in modulating the activity of mTORC1 through phosphorylation of Raptor Thr-908 and thus implicate a potential signaling mechanism by which ICK regulates cell proliferation and division
Koike-Kumagai et al., EMBO J 2009 : Moreover, TORC2 is essential for Trc phosphorylation on a residue that is critical for Trc activity in vivo and in vitro
Nölting et al., J Mol Endocrinol 2012 : Lovastatin alone significantly reduced MPC and MTT cell viability at therapeutically relevant doses and inhibited both ERK and AKT signalling, but increased mTORC1/p70S6K signalling ... Lovastatin alone significantly reduced MPC and MTT cell viability at therapeutically relevant doses and inhibited both ERK and AKT signalling, but increased mTORC1/p70S6K signalling
Dennis et al., J Biol Chem 2013 : These findings were extended to a cell culture system wherein loss of 4E-BP1 and 4E-BP2 resulted in elevated interaction of p70S6K1 with IGF1 induced activation of mTORC1 in conjunction with an enhanced rate of p70S6K1 phosphorylation at Thr-389 ... Together, these findings support the conclusion that, in the absence of 4E-BP proteins, mTORC1 mediated phosphorylation of p70S6K1 is elevated by a reduction in competition between the two substrates for interaction with raptor ... Together, these findings support the conclusion that, in the absence of 4E-BP proteins, mTORC1 mediated phosphorylation of p70S6K1 is elevated by a reduction in competition between the two substrates for interaction with raptor
Shimamura et al., Cancer Res 2008 (Adenocarcinoma...) : In contrast, Hsp90 inhibition overcomes these limitations in vitro and depletes cells of EGFR, other RTKs, and phospho-Akt and inhibits mTOR signaling whether or not T790M is present
Dickson , J Lipid Res 2008 (Inflammation) : Advances in understanding how the de novo synthesis of ceramide and complex sphingolipids is regulated have been made, and they demonstrate that the Target Of Rapamycin Complex 2 (TORC2) controls ceramide synthase activity ... The activity of Slm1 and Slm2 has also been shown to be regulated during heat stress by phosphoinositides and TORC2 , along with sphingoid long-chain bases and the Pkh1 and Pkh2 protein kinases, to control the actin cytoskeleton, the trafficking of nutrient transporters, and cell viability ... The activity of Slm1 and Slm2 has also been shown to be regulated during heat stress by phosphoinositides and TORC2 , along with sphingoid long-chain bases and the Pkh1 and Pkh2 protein kinases, to control the actin cytoskeleton, the trafficking of nutrient transporters, and cell viability
Amelio et al., Proc Natl Acad Sci U S A 2007 : Furthermore, TORC2 and NONO complex on cAMP-responsive promoters, and NONO acts as a bridge between the CREB/TORC complex and RNA polymerase II
Santini et al., J Biol Chem 2012 (MAP Kinase Signaling System...) : These studies demonstrate that, in D1R expressing MSNs, l-DOPA induced activation of ERK and mTORC1 requires DARPP-32 and indicates the importance of the cAMP/DARPP-32 signaling cascade in dyskinesia
Bonito-Oliva et al., Neuropharmacology 2013 : Haloperidol promotes mTORC1 dependent phosphorylation of ribosomal protein S6 via dopamine- and cAMP regulated phosphoprotein of 32 kDa and inhibition of protein phosphatase-1
Moore et al., J Biol Chem 2011 (MAP Kinase Signaling System) : In this study, we investigated the role of the mammalian target of rapamycin complex ( mTORC)-2 in Akt regulation using the recently identified small molecule ATP competitive mTOR inhibitors PP242 and Torin1
Yoon et al., J Cell Biol 2011 : Furthermore, amino acids stimulate PLD1 translocation to the lysosomal region where mTORC1 activation occurs in an hVps34 dependent manner, and this translocation is necessary for mTORC1 activation
Zhang et al., Proc Natl Acad Sci U S A 2012 : Taken together, these data reveal a signaling pathway by which phosphatidic acid synthesized via the glycerol-3-phosphate pathway inhibits mTORC2 activity by decreasing the association of rictor and mTOR , thereby down regulating insulin action
Dormond-Meuwly et al., Biochem Biophys Res Commun 2011 (Neoplasms...) : Downregulation of mTORC1 but not mTORC2 had similar effects showing that the inhibition of mTORC1 is responsible for the activation of MAPK ... Taken together these results show that blocking mTORC1 in endothelial cells activates MAPK and that a combined inhibition of MAPK and mTOR has additive anti-angiogenic effects
Woo et al., J Biol Chem 2007 (Breast Neoplasms...) : Despite no significant effect of PRR5 on mTORC2 mediated Akt phosphorylation, PRR5 silencing inhibits Akt and S6K1 phosphorylation and reduces cell proliferation rates, a result consistent with PRR5 roles in cell growth and tumorigenesis
Sancak et al., Science 2008 : Conversely, expression of a guanosine diphosphate bound Rag mutant prevented stimulation of mTORC1 by amino acids
Glidden et al., J Biol Chem 2012 : Although Rictor is required for the stability and activity of mTORC2 , little is known about functional regions or post-translational modifications within Rictor that are responsible for regulating mTORC2 ... p300 mediated acetylation of Rictor increases mTORC2 activity toward Akt, whereas site directed mutants within the acetylation region of Rictor exhibit reduced insulin-like growth factor 1 (IGF-1) stimulated mTORC2 kinase activity
Razmara et al., Cell communication and signaling : CCS 2013 : Inhibition of phosphatidylinositol 3-kinase (PI3K) inhibited PDGF-BB activation of both mTORC1 and mTORC2 ... Inhibition of phosphatidylinositol 3-kinase (PI3K) inhibited PDGF-BB activation of both mTORC1 and mTORC2 ... Inhibition of phosphatidylinositol 3-kinase (PI3K) inhibited PDGF-BB activation of both mTORC1 and mTORC2 ... Inhibition of phosphatidylinositol 3-kinase (PI3K) inhibited PDGF-BB activation of both mTORC1 and mTORC2 ... In addition, PDGF-BB induced activation of mTORC1 , as measured by phosphorylation of the downstream S6 protein, was dependent on phospholipase D ( PLD ) ... In addition, PDGF-BB induced activation of mTORC1 , as measured by phosphorylation of the downstream S6 protein, was dependent on phospholipase D ( PLD ) ... Thus, whereas both mTORC1 and mTORC2 are activated in a PI3K dependent manner, different additional signaling pathways are needed ... Thus, whereas both mTORC1 and mTORC2 are activated in a PI3K dependent manner, different additional signaling pathways are needed ... mTORC1 is activated in a PLD dependent manner and promotes phosphorylation of the S6 protein, whereas mTORC2 , in concert with PLC? signaling, promotes Akt phosphorylation ... mTORC1 is activated in a PLD dependent manner and promotes phosphorylation of the S6 protein, whereas mTORC2, in concert with PLC? signaling, promotes Akt phosphorylation
Sarkar et al., Mol Cell 2011 (Huntington Disease) : Additionally, NO inhibits IKKß and reduces AMPK phosphorylation, leading to mTORC1 activation via TSC2
Zhang et al., J Biol Chem 2010 (Glioblastoma) : Activation of AMP activated protein kinase by temozolomide contributes to apoptosis in glioblastoma cells via p53 activation and mTORC1 inhibition ... Our study suggests that activation of AMPK by TMZ contributes to glioblastoma cell apoptosis, probably by promoting p53 activation and inhibiting mTORC1 signaling
Pulakat et al., Am J Physiol Regul Integr Comp Physiol 2011 (Cardiovascular Diseases...) : We propose a scenario, whereby mTORC1-signaling mediated increase in AT2R expression in the INS-resistant ZO heart is a cardioprotective adaptation to overnutrition
Babcock et al., J Biol Chem 2013 : Although bortezomib induces eukaryotic initiating factor 2a phosphorylation, mTORC1 activity was also required for downstream induction of the UPR transcription factors ATF4 and CHOP by a mechanism involving increased expression of c-MYC ... Although bortezomib induces eukaryotic initiating factor 2a phosphorylation, mTORC1 activity was also required for downstream induction of the UPR transcription factors ATF4 and CHOP by a mechanism involving increased expression of c-MYC ... These findings indicate that the induction of ATF4/CHOP expression occurs via mTORC1 regulation of c-MYC and that this signaling pathway is a major determinant in the ability of bortezomib to induce apoptosis
Pracheil et al., J Biol Chem 2013 : It has been reported that protein phosphatase 2A (PP2A) and the Far3-7-8-9-10-11 complex ( Far complex ) negatively regulate TORC2 signaling in yeast
Bozulic et al., Curr Opin Cell Biol 2009 (Neoplasms) : This present review concerns PKB regulation by mTORC2 and DNA-PK in a stimulus dependent and context dependent manner and the possible implications of this for PKB activity, substrate specificity and therapeutic intervention
Carracedo et al., J Clin Invest 2008 (MAP Kinase Signaling System...) : Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K dependent feedback loop in human cancer ... Taken together, our findings identify MAPK activation as a consequence of mTORC1 inhibition and underscore the potential of a combined therapeutic approach with mTORC1 and MAPK inhibitors, currently employed as single agents in the clinic, for the treatment of human cancers
Tanaka et al., Clin Cancer Res 2011 (Neoplasms) : Effects on Akt phosphorylation induced by mTORC1 inhibition were tested with CH5132799 and compared with mTORC1 and PI3K/mTOR inhibitors
Montero et al., Mol Cancer Ther 2012 (Ovarian Neoplasms) : Therefore, mTORC1 probably controls p4E-BP1 along two distinct pathways, one of them sensitive to rapamycin and another insensitive
Chen et al., Mol Carcinog 2010 (Neoplasms) : In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors ... In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors ... In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors ... In this report, we focused on studying the role of mTORC1 and mTORC2 in rapamycin mediated Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors ... Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin mediated phosphorylation of Akt and ERK , and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin based therapeutic approaches in cancer cells ... Collectively, we conclude that mTORC2 plays a much more important role than mTORC1 in rapamycin mediated phosphorylation of Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin based therapeutic approaches in cancer cells
Li et al., J Biol Chem 2010 : In mammalian cells, uncontrolled activation of Rab5 and Arf1 strongly inhibit mTORC1 activity ... In mammalian cells, uncontrolled activation of Rab5 and Arf1 strongly inhibit mTORC1 activity ... Interestingly, the effect of Rab5 and Arf1 on mTORC1 is specific to amino acid stimulation, whereas glucose induced mTORC1 activation is not blocked by Rab5 or Arf1 ... Interestingly, the effect of Rab5 and Arf1 on mTORC1 is specific to amino acid stimulation, whereas glucose induced mTORC1 activation is not blocked by Rab5 or Arf1 ... Similarly, active Rab5 selectively inhibits mTORC1 activation by Rag GTPases, which are involved in amino acid signaling, but does not inhibit the effect of Rheb , which directly binds and activates mTORC1 ... Similarly, active Rab5 selectively inhibits mTORC1 activation by Rag GTPases, which are involved in amino acid signaling, but does not inhibit the effect of Rheb, which directly binds and activates mTORC1
Wang et al., Diabetes 2013 (Diabetes Mellitus) : Further, inhibition of miR-7a activates mTOR signaling and promotes adult ß-cell replication in mouse primary islets, which can be reversed by the treatment with a well-known mTOR inhibitor, rapamycin
Jung et al., Mol Biol Cell 2009 : ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery ... ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery ... ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery ... These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling ... These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling ... These findings demonstrate that the ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in response to mTOR signaling
Dunaway et al., Mol Cell Biol 2011 : Slit2 stimulates angiogenesis through mTORC2 dependent activation of Akt and Rac GTPase, the activities of which are inhibited in the presence of ephrin-A1 ... Slit2 stimulates angiogenesis through mTORC2 dependent activation of Akt and Rac GTPase, the activities of which are inhibited in the presence of ephrin-A1
Jiang et al., Am J Pathol 2008 (Angiomyolipoma...) : Together, these data show that mTORC1 activity is insufficient for increased glycolysis in tumors and that constitutive mTOR activity negatively regulates glucose transporter trafficking
Roux et al., Proc Natl Acad Sci U S A 2004 (MAP Kinase Signaling System...) : Phosphatidylinositol 3-kinase (PI3K) inactivates the tumor suppressor complex and enhances mTOR signaling by means of phosphorylation of tuberin by Akt
Wong et al., J Biol Chem 2010 : Inhibition of AMPK prevented translation repression by cordycepin and abolished 4EBP1 dephosphorylation, indicating that the effect of cordycepin on mTOR signaling and protein synthesis is mediated by AMPK activation
James et al., Mol Cell Biol 2009 (Meningioma...) : Merlin does not regulate mTORC1 via the established mechanism of phosphoinositide 3-kinase-Akt or mitogen activated protein kinase/extracellular signal regulated kinase mediated TSC2 inactivation and may instead regulate TSC/mTOR signaling in a novel fashion ... Merlin does not regulate mTORC1 via the established mechanism of phosphoinositide 3-kinase-Akt or mitogen activated protein kinase/extracellular signal regulated kinase mediated TSC2 inactivation and may instead regulate TSC/mTOR signaling in a novel fashion
Balgi et al., PloS one 2009 : TSC2 , a negative regulator of mTORC1, was required for inhibition of mTORC1 signaling by rottlerin but not for mTORC1 inhibition by perhexiline, niclosamide and amiodarone ... Transient exposure of immortalized mouse embryo fibroblasts to these drugs was not toxic in nutrient-rich conditions but led to rapid cell death by apoptosis in starvation conditions, by a mechanism determined in large part by the tuberous sclerosis complex protein TSC2 , an upstream regulator of mTORC1
López-Lago et al., Mol Cell Biol 2009 (Mesothelioma) : Loss of the tumor suppressor gene NF2 , encoding merlin, constitutively activates integrin dependent mTORC1 signaling
Jung et al., J Toxicol Sci 2012 : In conclusion, OA increases the proliferation and decreases the starvation induced apoptosis of SK-Hep1 cells via mTORC1 activation mediated by negative regulation of AMPK
Wang et al., PloS one 2013 : Western blotting showed that the PP242 inhibition of mTORC2 mediated AKT phosphorylation at Ser 473 ( AKT ( S473 ) ) was transient only in the first few hours of the PP242 treatment ... The parallel increase of AKT ( S473 ) and EGFR ( T1068 ) in the cells following PP242 treatment raised the possibility that EGFR phosphorylation might contribute to the PP242 incomplete inhibition of mTORC2
Winter et al., Am J Physiol Cell Physiol 2011 : Previous studies have shown that, in part, Akt and ERK promote mTORC1 signaling through phosphorylation of a GTPase activator protein (GAP), referred to as tuberous sclerosis complex 2 (TSC2), that acts as an upstream inhibitor of mTORC1 ... Previous studies have shown that, in part, Akt and ERK promote mTORC1 signaling through phosphorylation of a GTPase activator protein (GAP), referred to as tuberous sclerosis complex 2 (TSC2), that acts as an upstream inhibitor of mTORC1
Haas et al., Cell Metab 2012 (Diabetes Mellitus, Type 2...) : Liver insulin receptor knockout ( LIRKO ) mice show that in the physiological context of feeding, hepatic insulin signaling is not required for the induction of mTORC1 , an upstream activator of the lipogenic regulator, SREBP-1c
Alexander et al., Cell cycle (Georgetown, Tex.) 2010 : We found that TSC2 activation results in mTORC1 repression and subsequent induction of autophagy
Magnuson et al., Biochem J 2012 : mTORC1 ( mammalian TORC1 ) phosphorylates and activates S6K1 and S6K2, whose first identified substrate was rpS6 ( ribosomal protein S6 ), a component of the 40S ribosome ... mTORC1 ( mammalian TORC1 ) phosphorylates and activates S6K1 and S6K2 , whose first identified substrate was rpS6 ( ribosomal protein S6 ), a component of the 40S ribosome
Gulhati et al., Cancer Res 2011 (Colorectal Neoplasms...) : mTORC1 and mTORC2 regulate EMT , motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways ... mTORC1 and mTORC2 regulate EMT , motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways
Ryu et al., Cell Metab 2009 (Glucose Intolerance...) : TORC2 regulates hepatic insulin signaling via a mammalian phosphatidic acid phosphatase, LIPIN1
Werzowa et al., Br J Dermatol 2009 (Melanoma...) : Inhibition of mTORC2 led to reduced levels of phosphorylated AKT
Hayashi et al., Am J Physiol Endocrinol Metab 2007 : Consistent with this, GH increased the phosphorylation of TSC2 , an upstream regulator of mTORC1 , at sites that are targets for Akt/PKB
Tzatsos , J Biol Chem 2009 : Overall, these data provide new insights in the molecular mechanisms by which mTORC1 inhibits PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaffold dependent ... Overall, these data provide new insights in the molecular mechanisms by which mTORC1 inhibits PI 3-kinase/Akt signaling at the level of IRS-1 and suggest that mTOR signaling toward Akt is scaffold dependent
Maehama et al., J Biol Chem 2008 : In addition, RalA knockdown suppressed Rheb induced S6 kinase phosphorylation, and the constitutively active form of RalA induced mTORC1 activation in the absence of Rheb
Arous et al., Diabetologia 2011 : Oleate mediated mTORC1 activation required phospholipase D activation, which produces phosphatidic acid and is known to render mTORC1 rapamycin resistant
Nishioka et al., Int J Cancer 2009 (Leukemia, Myeloid, Acute) : ATRA ( 0.1-1 microM ) upregulated levels of RTP801 , a negative regulator of mTORC1, and inhibited mTORC1 signaling as assessed by measurement of the levels of p-p70S6K and p-4E-BP1 in HL60 and NB4 cells
McGhee et al., J Nutr 2009 (Diabetes Mellitus, Experimental...) : Overall, the results demonstrate that changes in REDD1 expression likely contribute to the regulation of mTORC1 signaling during food deprivation and refeeding
Melnik , J Obes 2012 : Leucine thus functions as a maternal-neonatal relay for mTORC1 dependent neonatal ß-cell proliferation and insulin secretion
Li et al., J Ethnopharmacol 2012 (Arthritis, Experimental) : To investigate the role of PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R in antibodies production and the regulation of Pae on the signaling pathway in rats with collagen induced arthritis ( CIA ) ... To investigate the role of PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R in antibodies production and the regulation of Pae on the signaling pathway in rats with collagen induced arthritis ( CIA ) ... PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R participates in antibodies production by B lymphocytes of CIA rats ... PI3K/Akt/mTOR signaling mediated by BAFF/BAFF-R participates in antibodies production by B lymphocytes of CIA rats
Sancak et al., Mol Cell 2007 : Insulin stimulates Akt/PKB mediated phosphorylation of PRAS40, which prevents its inhibition of mTORC1 in cells and in vitro
Durán et al., Mol Cell 2012 : Inhibition of glutaminolysis prevented GTP loading of RagB and lysosomal translocation and subsequent activation of mTORC1 ... Constitutively active Rag heterodimer activated mTORC1 in the absence of glutaminolysis ... Thus, mTORC1 senses and is activated by glutamine and leucine via glutaminolysis and a-ketoglutarate production upstream of Rag
Gibbons et al., Semin Oncol 2009 (Neoplasms) : Activated mTORC1 regulates protein synthesis by directly phosphorylating 4E-binding protein 1 (4E-BP1) and p70S6K ( S6K ), translation initiation factors that are important to cap dependent mRNA translation, which increases the level of many proteins that are needed for cell cycle progression, proliferation, angiogenesis, and survival pathways ... Activated mTORC1 regulates protein synthesis by directly phosphorylating 4E-binding protein 1 (4E-BP1) and p70S6K ( S6K ), translation initiation factors that are important to cap dependent mRNA translation, which increases the level of many proteins that are needed for cell cycle progression, proliferation, angiogenesis, and survival pathways
Wang et al., Lipids in health and disease 2012 (Obesity) : HDL and apoA-I could activate PI3K-Akt-mTORC1 signaling which negatively regulates autophagy
Gan et al., Cancer Cell 2010 (Carcinoma, Renal Cell...) : mTORC1 is a validated therapeutic target for renal cell carcinoma (RCC)
Wander et al., J Clin Invest 2011 (Neoplasms) : While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers
Kucejova et al., Mol Cancer Res 2011 (Carcinoma, Renal Cell) : REDD1 is upregulated by hypoxia-inducible factor (HIF)-1 , and forced REDD1 expression is sufficient to inhibit mTORC1 ... REDD1 is upregulated by hypoxia-inducible factor (HIF)-1, and forced REDD1 expression is sufficient to inhibit mTORC1 ... REDD1 induced mTORC1 inhibition is dependent on a protein complex formed by the tuberous sclerosis complex (TSC)1 and 2 ( TSC2 ) proteins ... In clear-cell renal cell carcinoma ( ccRCC ), the von Hippel-Lindau (VHL) gene is frequently inactivated leading to constitutive activation of HIF-2 and/or HIF-1, which may be expected to upregulate REDD1 and inhibit mTORC1 ... Understanding how ccRCCs become refractory to REDD1 induced mTORC1 inhibition should shed light into the development of ccRCC and may aid in patient selection for molecular targeted therapies
Bahl et al., Molecular autism 2013 : Pam, an E3 ubiquitin ligase, binds to TSC proteins and regulates mTORC1 signaling in the CNS, and the FBXO45-Pam ubiquitin ligase complex plays an essential role in neurodevelopment by regulating synapse formation and growth ... Pam , an E3 ubiquitin ligase, binds to TSC proteins and regulates mTORC1 signaling in the CNS, and the FBXO45-Pam ubiquitin ligase complex plays an essential role in neurodevelopment by regulating synapse formation and growth
Wang et al., Science signaling 2009 (Cardiovascular Diseases...) : Rapamycin treatment of diet induced obese mice or of transgenic mice with long-term activation of endothelial Akt inhibits activation of mammalian target of rapamycin (mTOR)-rictor complex 2 and Akt, prevents vascular senescence without altering body weight, and reduces the severity of limb necrosis and ischemic stroke
Avruch et al., Am J Physiol Endocrinol Metab 2009 : Insulin , growth factors, and a variety of cellular stressors regulate mTORC1 by controlling Rheb GTP charging through modulating the activity of the tuberous sclerosis complex, the Rheb GTPase activating protein ... In contrast, amino acids, especially leucine, regulate mTORC1 by controlling the ability of Rheb-GTP to activate mTORC1 ... The rag heterodimer interacts directly with mTORC1 and may direct mTORC1 to the Rheb containing vesicular compartment in response to amino acid sufficiency, enabling Rheb-GTP activation of mTORC1
Kim et al., Mol Cell 2012 : Here, we found that mTORC2 can also regulate insulin signaling at the level of insulin receptor substrate-1 (IRS-1) ... Our findings reveal that in addition to persistent mTORC1 signaling, heightened mTORC2 signals can promote insulin resistance due to mTORC2 mediated degradation of IRS-1
Matsui et al., EMBO Rep 2013 : Rab12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4 ... Knockdown of Rab12 results in inhibition of autophagy and in increased activity of mTORC1 ( mammalian/mechanistic target of rapamycin complex 1 ), an upstream regulator of autophagy
Misra et al., J Cell Biochem 2012 (Prostatic Neoplasms) : We measured mTORC2 dependent Akt phosphorylation at S473 in immunoprecipitates of mTOR or Rictor from 1-LN cells ... These studies represent the first report that Epac1 mediates mTORC2 dependent phosphorylation of Akt ( S473 ) ... We further demonstrate that in 8-CPT-2Me-cAMP treated cells, Epac1 co-immunoprecipitates with AKAP, Raptor, Rictor, PDE3B, and PDE4D suggesting thereby that during Epac1 induced activation of mTORC1 and mTORC2, Epac1 may have an additional function as a `` scaffold '' protein ... We further demonstrate that in 8-CPT-2Me-cAMP treated cells, Epac1 co-immunoprecipitates with AKAP, Raptor, Rictor, PDE3B, and PDE4D suggesting thereby that during Epac1 induced activation of mTORC1 and mTORC2 , Epac1 may have an additional function as a `` scaffold '' protein
Ramírez-Valle et al., Mol Cell Biol 2010 : Mitotic raptor promotes mTORC1 activity, G ( 2 ) /M cell cycle progression, and internal ribosome entry site mediated mRNA translation
Jung et al., J Nutr Biochem 2013 : The results suggested that fisetin treatment inhibits mTORC1 activity in an Akt dependent manner
Harston et al., Am J Physiol Heart Circ Physiol 2011 (Hypertrophy) : Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes : mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival ... Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes : mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and mTORC2 that activates Akt to promote cell survival
Tamai et al., J Biol Chem 2013 (Hypertrophy) : Thus, Rheb dependent mTORC1 activation becomes essential for cardiomyocyte hypertrophic growth after early postnatal period
Chiu et al., Amino Acids 2012 : Thus, glutamine stimulates mTORC1 independent of cell leucine, suggesting the existence of two distinct stimulatory signals from either glutamine or EAA
Goncharova et al., Mol Cell Biol 2011 : Our data demonstrate that mTORC2 dependent activation of RhoA is required for TSC2-null cell growth and survival and suggest that targeting both mTORC2 and mTORC1 by a combination of proapoptotic simvastatin and cytostatic rapamycin shows promise for combinational therapeutic intervention in diseases with TSC2 dysfunction
Huang et al., Cancer Lett 2009 (Carcinoma...) : Also, we found blockage mTORC1 inhibited Cyclin D1 expression in CNE-2 cells and enhanced cell apoptosis
Palazuelos et al., J Biol Chem 2012 : Likewise, CB(2) receptor engagement induced cell proliferation in an mTORC1 dependent manner both in embryonic cortical slices and in adult hippocampal NPs
Watterson et al., Neurosignals 2013 (Anorexia) : Insulin and leptin increase mTORC1 activity in a phosphoinositide-3-kinase (PI3K)- and protein kinase B (PKB) dependent manner, compared to vehicle controls, whereas increasing AMPK activity inhibits mTORC1 activity and blocks the actions of the anorexigenic hormones ... Ghrelin mediates an AMPK dependent decrease in mTORC1 activity and increases hypothalamic AgRP mRNA levels, the latter effect being prevented by insulin in an mTORC1 dependent manner ... Ghrelin mediates an AMPK dependent decrease in mTORC1 activity and increases hypothalamic AgRP mRNA levels, the latter effect being prevented by insulin in an mTORC1 dependent manner
Kenerson et al., Gastroenterology 2013 (Carcinoma, Hepatocellular...) : In livers of albumin (Alb)-Cre mice, we selectively deleted tuberous sclerosis (Tsc)1 , a negative regulator of Ras homolog enriched in brain and mTORC1 , along with Phosphatase and tensin homolog (Pten), a negative regulator of PI3K
O'Brien et al., Eur J Immunol 2011 : The TSC1/TSC2 complex has been shown to inhibit mTORC1 signaling in cell line models ... Overall, our results demonstrate that TSC1 differentially regulates mTORC1 and mTORC2 activity, promotes T-cell survival, and is critical for normal mitochondrial homeostasis in T cells ... Overall, our results demonstrate that TSC1 differentially regulates mTORC1 and mTORC2 activity, promotes T-cell survival, and is critical for normal mitochondrial homeostasis in T cells
Wong et al., Biochem Biophys Res Commun 2013 : Thus, we found that inhibiting mTORC1 dependent 4E-BP1 phosphorylation mimics the effect of hypoxia on TXNIP expression
Uhlenbrock et al., FEBS Lett 2009 : Recent studies document that Rheb activates mTORC1 via direct, GTP dependent interaction with the peptidyl-prolyl-cis/trans-isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1 ... Cell biological experiments illustrate that FKBP38 plays only a very minor, if any, role in mTORC1 activation
Yoshida et al., J Biol Chem 2011 : Taken together, our results suggest that the TSC complex plays an important role in redox-sensitive mTORC1 regulation and argues for the activation of mTORC1 in places other than the lysosome upon inhibition of the TSC complex
Meikle et al., J Neurosci 2008 (Disease Models, Animal...) : Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors : effects on mTORC1 and Akt signaling lead to improved survival and function ... We have tested rapamycin and RAD001 [ 40-O- ( 2-hydroxyethyl ) -rapamycin ], both mammalian target of rapamycin mTORC1 inhibitors , as potential therapeutic agents in this model
Jin et al., Cancer Lett 2013 (Lung Neoplasms) : Herein, we show that the constitutive overexpression of Redd1 , a negative regulator of mTORC1 , induces Akt activation in lung cancer cells ... Therefore, the sustained overexpression of Redd1 leads to mTORC1 inhibition and to consequent Akt activation that is involved in cell survival
Shrivastava et al., Mol Cancer Ther 2011 (Breast Neoplasms) : We showed that CBD induces endoplasmic reticulum stress and, subsequently, inhibits AKT and mTOR signaling as shown by decreased levels of phosphorylated mTOR and 4EBP1, and cyclin D1
Jeon et al., Biochim Biophys Acta 2013 (Breast Neoplasms...) : When SelW was down-regulated, mTORC2 dependent phosphorylation of Akt at Ser473 was decreased
Julien et al., Mol Cell Biol 2010 : While mTOR complex 1 (mTORC1) regulates mRNA translation and ribosome biogenesis, mTORC2 plays an important role in the phosphorylation and subsequent activation of Akt ... Interestingly, mTORC1 negatively regulates Akt activation, but whether mTORC1 signaling directly targets mTORC2 remains unknown ... We found that Rictor phosphorylation requires mTORC1 activity and, more specifically, the p70 ribosomal S6 kinase 1 ( S6K1 ) ... However, cells expressing a Rictor T1135A mutant were found to have increased mTORC2 dependent phosphorylation of Akt ... In addition, phosphorylation of the Akt substrates FoxO1/3a and glycogen synthase kinase 3 alpha/beta ( GSK3 alpha/beta ) was found to be increased in these cells, indicating that S6K1 mediated phosphorylation of Rictor inhibits mTORC2 and Akt signaling
Roca et al., Neoplasia (New York, N.Y.) 2009 (Prostatic Neoplasms) : D942, a pharmacological activator of AMPK, stunted CCL2 induced mTORC1 activity, survivin expression, and cell survival without significantly affecting Akt activity
Rhein et al., Ann Hematol 2011 (Leukemia, Experimental) : However, Rapamycin did not completely inhibit mTORC1 dependent phosphorylation of 4E-BP1
Lazorchak et al., Protein & cell 2011 (Cell Transformation, Neoplastic) : We also propose a novel strategy to treat cancers based on our recent discovery that mTORC2 regulates Akt protein stability
Partovian et al., Mol Cell 2008 : Reduced mTORC2 activity in S4 ( -/- ) endothelial cells results in decreased FoxO1/3a and eNOS phosphorylation, decreased endothelial cell size, and increased arterial blood pressure in S4 ( -/- ) mice ... Reduced mTORC2 activity in S4 ( -/- ) endothelial cells results in decreased FoxO1/3a and eNOS phosphorylation, decreased endothelial cell size, and increased arterial blood pressure in S4 ( -/- ) mice
Wenner , J Cell Physiol 2012 (Neoplasms) : In addition, chemotherapeutic approaches based on Akt activated mTORC1 are described, and their relationship to the role of aerobic glycolysis in this protection
Gulhati et al., Carcinogenesis 2012 (Colorectal Neoplasms...) : In this study, we show that inhibition of mTORC1 with rapamycin leads to feedback activation of PI3K/Akt and Ras-MAPK signaling, resulting in cell survival and possible contribution to rapamycin resistance ... In this study, we show that inhibition of mTORC1 with rapamycin leads to feedback activation of PI3K/Akt and Ras-MAPK signaling, resulting in cell survival and possible contribution to rapamycin resistance ... In this study, we show that inhibition of mTORC1 with rapamycin leads to feedback activation of PI3K/Akt and Ras-MAPK signaling, resulting in cell survival and possible contribution to rapamycin resistance
Zhang et al., Breast Cancer Res Treat 2012 (Breast Neoplasms) : Although NDGA stimulated AMP activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2) signaling, which negatively regulates mTORC1, AMPK and TSC2 deletion could not diminish the inhibition of mTORC1 by NDGA ... Although NDGA stimulated AMP activated protein kinase (AMPK)/tuberous sclerosis complex 2 (TSC2) signaling, which negatively regulates mTORC1, AMPK and TSC2 deletion could not diminish the inhibition of mTORC1 by NDGA ... Subsequent studies revealed that NDGA may also direct target mTORC1 complex because NDGA suppressed amino acids- and insulin stimulated mTORC1 and acted like rapamycin to disrupt mTOR-Raptor interaction ... Disruption of mTOR-Raptor complex and activation of AMPK/TSC signaling may contribute to inhibitory effects of NDGA against mTORC1 ... Disruption of mTOR-Raptor complex and activation of AMPK/TSC signaling may contribute to inhibitory effects of NDGA against mTORC1
Deshmukh et al., Mol Endocrinol 2008 : However, in WT mice, preincubation with AICAR completely inhibited insulin induced phosphorylation of mTOR targets, suggesting mTOR signaling is blocked by prior AMPK activation
Jones et al., PLoS Biol 2009 : These findings identify new physiological roles for TORC2 , mediated by SGK , in regulation of C. elegans lipid accumulation and growth, and they challenge the notion that AKT is the primary effector of TORC2 function
Hall et al., Breast Cancer Res Treat 2012 (Breast Neoplasms) : Previous studies have alternatively suggested that either mTORC1 or mTORC2 is exclusively required for SGK1 's Ser422 phosphorylation and activation in breast cancer cells ... Previous studies have alternatively suggested that either mTORC1 or mTORC2 is exclusively required for SGK1 's Ser422 phosphorylation and activation in breast cancer cells
Rodrik-Outmezguine et al., Cancer Discov 2011 : mTOR kinase inhibitors block mTORC1 and mTORC2 and thus do not cause the mTORC2 activation of AKT observed with rapamycin ... mTOR kinase inhibitors block mTORC1 and mTORC2 and thus do not cause the mTORC2 activation of AKT observed with rapamycin ... mTOR kinase inhibitors block mTORC1 and mTORC2 and thus do not cause the mTORC2 activation of AKT observed with rapamycin ... Inhibition of mTORC2 leads to AKT serine 473 ( S473 ) dephosphorylation and a rapid but transient inhibition of AKT T308 phosphorylation and AKT signaling
Liu et al., J Neuroendocrinol 2011 : The demonstration that TORC2 translocates to the nucleus of hypothalamic CRH neurones and interacts with the CRH promoter in conjunction with the activation of CRH transcription during restraint stress, provides strong evidence for the involvement of TORC2 in the physiological regulation of CRH transcription
Guo et al., Mol Cancer Res 2013 : Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1 ... Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1
Wang et al., J Mol Cell Cardiol 2008 (Cardiomegaly) : Ras homolog enriched in brain (Rheb) positively regulates mTORC1 ... Overexpression of Rheb in ARVC activated mTORC1 signaling, several components of the translational machinery and stimulated protein synthesis
Horak et al., Proc Natl Acad Sci U S A 2010 (Cell Transformation, Viral...) : Surprisingly, however, HIF-1 up-regulation in REDD1 ( -/- ) cells is largely independent of mTORC1 activity
Fujishita et al., Cell cycle (Georgetown, Tex.) 2009 (Adenoma...) : We have recently found that the mTORC1 pathway is activated in intestinal adenomas of Apc mutant mice, accompanied by an elevated level of mTOR protein, and that treatment with RAD001 , an mTORC1 inhibitor , suppresses the growth of these polyps
Wong et al., Curr Opin Pharmacol 2010 (Metabolic Diseases) : SREBP-1c can be induced by mTORC1 , bifurcating lipogenesis from AKT activated gluconeogenesis
Martina et al., J Cell Biol 2013 : Interaction of TFEB with active Rag heterodimers promoted recruitment of TFEB to lysosomes, leading to mTORC1 dependent phosphorylation and inhibition of TFEB
Pearce et al., Biochem J 2011 : Both complexes phosphorylate the hydrophobic motifs of AGC kinase family members : mTORC1 phosphorylates S6K ( S6 kinase ), whereas mTORC2 regulates phosphorylation of Akt, PKCa ( protein kinase Ca ) and SGK1 ( serum- and glucocorticoid induced protein kinase 1 ) ... Both complexes phosphorylate the hydrophobic motifs of AGC kinase family members : mTORC1 phosphorylates S6K ( S6 kinase ), whereas mTORC2 regulates phosphorylation of Akt , PKCa ( protein kinase Ca ) and SGK1 ( serum- and glucocorticoid induced protein kinase 1 ) ... Taken together, these results suggest that Protor-1 may play a role in enabling mTORC2 to efficiently activate SGK1 , at least in the kidney
Fournier et al., Mol Cell Biol 2013 : mTORC1 specifically drives the eIF4E mediated formation of SG through the phosphorylation of 4E-BP1, a key factor known to inhibit formation of the mTORC1 dependent eIF4E-eIF4GI interactions
Wahdan-Alaswad et al., Mol Cancer Res 2012 (Prostatic Neoplasms) : Intriguingly, silencing raptor alone enhanced, whereas silencing rictor repressed, the phosphorylation of Smad1/5, indicating that mTORC1 represses, whereas mTORC2 activates , BMP signaling
Li et al., J Biol Chem 2013 : In Drosophila S2 cells and mammalian cells, knockdown of MARK family member increased mTORC1 activity, whereas overexpression of MARK4 in mammalian cells significantly inhibited mTORC1 activity ... Interestingly, MARK4 selectively inhibits mTORC1 activation by Rag GTPases, which are involved in amino acid signaling, but does not inhibit the effect of Rheb , which directly binds to and activates mTORC1 ... Interestingly, MARK4 selectively inhibits mTORC1 activation by Rag GTPases, which are involved in amino acid signaling, but does not inhibit the effect of Rheb, which directly binds to and activates mTORC1 ... Interestingly, MARK4 selectively inhibits mTORC1 activation by Rag GTPases, which are involved in amino acid signaling, but does not inhibit the effect of Rheb, which directly binds to and activates mTORC1
Breuleux et al., Mol Cancer Ther 2009 (Neoplasms) : RAD001 ( everolimus ), an mTORC1 ( mTOR/raptor ) inhibitor , has broad antitumor activity in preclinical models and cancer patients ... Strikingly, rictor down-regulation attenuated AKT S473 phosphorylation induced by mTORC1 inhibition
Settembre et al., EMBO J 2012 : Conversely, pharmacological inhibition of mTORC1 , as well as starvation and lysosomal disruption, activates TFEB by promoting its nuclear translocation ... Interestingly, the Rag GTPase complex, which senses lysosomal amino acids and activates mTORC1 , is both necessary and sufficient to regulate starvation- and stress induced nuclear translocation of TFEB
Brito et al., Atherosclerosis 2009 (Atherosclerosis) : The activation of mTOR signaling by oxLDL, requires the upstream activation of PI3K and Akt , as assessed by the inhibitory effect of the PI3K inhibitor Ly294002 on mTOR activation and DNA synthesis ... The activation of mTOR signaling by oxLDL, requires the upstream activation of PI3K and Akt, as assessed by the inhibitory effect of the PI3K inhibitor Ly294002 on mTOR activation and DNA synthesis
Xu et al., J Biol Chem 2011 : Amino acid- and glucose induced PLD and mTORC1 activity were also dependent on the GTPases RalA and ARF6 and the type III phosphatidylinositol-3-kinase hVps34 ... Amino acid- and glucose induced PLD and mTORC1 activity were also dependent on the GTPases RalA and ARF6 and the type III phosphatidylinositol-3-kinase hVps34 ... Amino acid- and glucose induced PLD and mTORC1 activity were also dependent on the GTPases RalA and ARF6 and the type III phosphatidylinositol-3-kinase hVps34
Mansley et al., Br J Pharmacol 2010 : TORC2 , but not TORC1, is also involved in glucocorticoid induced SGK1 activation but its role is permissive
Huang et al., Biochem Soc Trans 2009 : Through negative-feedback mechanisms, mTORC1 activity inhibits growth factor stimulation of PI3K
Wang et al., Cancer Res 2008 (Lung Neoplasms) : The present work focused on addressing the role of mTOR/rictor in mTOR inhibitor induced Akt activation and the effect of sustained Akt activation on mTOR targeted cancer therapy ... Collectively, we conclude that inhibition of the mTOR/raptor complex initiates Akt activation independent of mTOR/rictor
Jung et al., Autophagy 2011 : ULK1 inhibits the kinase activity of mTORC1 and cell proliferation ... ( 1-3 ) Here, we investigated how ULK1 regulates mTORC1 signaling, and found that ULK1 inhibits the kinase activity of mTORC1 and cell proliferation ... Deficiency or knockdown of ULK1 or its homolog ULK2 enhanced mTORC1 signaling, cell proliferation rates and accumulation of cell mass, whereas overexpression of ULK1 had the opposite effect ... The stimulatory effect of ULK1 knockdown on mTORC1 signaling occurred even in the absence of tuberous sclerosis complex 2 (TSC2) , the negative regulator of mTORC1 signaling ... In addition, ULK1 was found to bind raptor, induce its phosphorylation, and inhibit the kinase activity of mTORC1 ... In addition, ULK1 was found to bind raptor , induce its phosphorylation, and inhibit the kinase activity of mTORC1 ... In addition, ULK1 was found to bind raptor, induce its phosphorylation, and inhibit the kinase activity of mTORC1 ... These results demonstrate that ULK1 negatively regulates the kinase activity of mTORC1 and cell proliferation in a manner independent of Atg5 and TSC2
Chong et al., Oxidative medicine and cellular longevity 2010 (Neurodegenerative Diseases) : The function of mTOR signaling is mediated primarily through two mTOR complexes : mTORC1 and mTORC2 ... The function of mTOR signaling is mediated primarily through two mTOR complexes : mTORC1 and mTORC2
Xie et al., Cell Signal 2011 : In this study, we show that the pharmacological elevation of [ cAMP ] ( i ) in mouse embryonic fibroblasts ( MEFs ) and human embryonic kidney 293 (HEK293) cells inhibits mTORC1 activation via a PKA dependent mechanism ... We provide evidence that this cAMP dependent inhibition of mTORC1/2 is caused by the dissociation of mTORC1 and 2 and a reduction in mTOR catalytic activity, as determined by its auto-phosphorylation on Ser2481
Høyer-Hansen et al., Autophagy 2007 (Calcium Signaling) : The present study suggests hat AMPK inhibits mTORC1 and autophagy also in nonstarved cells
Salles et al., J Neurochem 2013 : Transient and rapid activation of Akt/GSK-3ß and mTORC1 signaling by D3 dopamine receptor stimulation in dorsal striatum and nucleus accumbens
Fujishita et al., Proc Natl Acad Sci U S A 2008 (Adenoma...) : These results suggest that the Wnt signaling contributes to mTORC1 activation through the increased level of mTOR and that the activation plays important roles in the intestinal polyp formation and growth
Prizant et al., J Cell Biochem 2008 : This confirms specific mTORC1 regulation of S6K1 phosphorylation
Li et al., Am J Physiol Cell Physiol 2011 (MAP Kinase Signaling System) : mTORC1 inhibition increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON ... Here, we demonstrate that the inhibition of mTORC1 by rapamycin ( mTORC1 inhibitor ), torin1 ( both mTORC1 and mTORC2 inhibitor ) or short hairpin RNA mediated knockdown of mTOR, regulatory associated protein of mTOR ( RAPTOR ), and p70 S6 kinase (p70S6K) increased basal NT release via upregulating NT gene expression in BON cells
Yan et al., J Cell Biochem 2010 : VEGF stimulation results in mTOR signaling activation which changes the phosphorylation status of 4E-BP1, the downstream of mTOR signaling, and ultimately contributes to the translation initiation of Livin protein
Burgos et al., Domest Anim Endocrinol 2010 : In addition, IGF-1 stimulated mTORC1 kinase activity toward 4E-BP1 in vitro
Knizhnik et al., J Cell Biochem 2012 (MAP Kinase Signaling System...) : Namely, we showed that Arf6 in a PLD-mTORC1 dependent manner activates S6K1 kinase, a well-known regulator of mitogen stimulated translation initiation
Huang et al., Cancer Res 2009 (Angiomyolipoma...) : We also show that the TSC1-TSC2 complex can directly stimulate the in vitro kinase activity of mTORC2
Canettieri et al., Cell Metab 2005 : Dual role of the coactivator TORC2 in modulating hepatic glucose output and insulin signaling ... Here, we show that, in parallel with their effects on glucose output, CREB and TORC2 also enhance insulin signaling in liver by stimulating expression of the insulin receptor substrate 2 (IRS2) gene
Peterson et al., Cell 2009 (Multiple Myeloma) : Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities ... Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities
Schwarz et al., Circ Res 2009 (Disease Models, Animal...) : These results strongly indicate that CXCR3 dependent activation of mTORC1 directly links stimulation of the Th1 immune system with the proliferative response of intimal cells in vascular remodeling
Parrales et al., Cell Signal 2013 : ERK1/2 dependent activation of mTOR/mTORC1/p70S6K regulates thrombin induced RPE cell proliferation ... Since Akt functions as an upstream activator of mechanistic target of rapamycin complex 1 ( mTORC1 ) and is also a downstream target for mTORC2 , the aim of this work was to determine whether mTOR is involved in thrombin induced RPE cell proliferation by regulating cyclin D1 expression in immortalized rat RPE-J cell line
Kaur et al., Proc Natl Acad Sci U S A 2012 : We provide evidence that mTORC2 complexes control IFN induced phosphorylation of AKT on serine 473 and their function is ultimately required for IFN dependent gene transcription via interferon stimulated response elements
Najafov et al., Biochem J 2012 (Neoplasms) : Akt is activated by phosphorylation of its T-loop residue ( Thr ( 308 ) ) by PDK1 ( 3-phosphoinositide dependent kinase-1 ) and its C-terminal hydrophobic motif ( Ser ( 473 ) ) by mTORC2 [ mTOR ( mammalian target of rapamycin ) complex 2 ] ... Akt is activated by phosphorylation of its T-loop residue ( Thr ( 308 ) ) by PDK1 ( 3-phosphoinositide dependent kinase-1 ) and its C-terminal hydrophobic motif ( Ser ( 473 ) ) by mTORC2 [ mTOR ( mammalian target of rapamycin ) complex 2 ]
Toschi et al., J Biol Chem 2008 : These data indicate that although HIF1 alpha is dependent on both mTORC1 and mTORC2, HIF2 alpha is dependent only on mTORC2 ... These data indicate that although HIF1 alpha is dependent on both mTORC1 and mTORC2 , HIF2 alpha is dependent only on mTORC2 ... These data indicate that although HIF1 alpha is dependent on both mTORC1 and mTORC2, HIF2 alpha is dependent only on mTORC2
Timmerman et al., J Clin Endocrinol Metab 2010 : During insulin infusion, blood flow and capillary recruitment increased in the control ( P < 0.05 ) group only ; Akt phosphorylation and glucose uptake increased in both groups ( P < 0.05 ), with no group differences ; and mTORC1 signaling increased more in control ( P < 0.05 ) than in L-NMMA
Xu et al., Dev Dyn 2009 : It is proposed that mTORC1 may be involved in the control of MPF by regulating S6K1 during the early development of mouse embryos
Shanmugasundaram et al., Oncogene 2013 (Carcinoma, Renal Cell...) : Here we provide additional genetic evidence that PI3K signaling activates mTORC2 kinase activity ... We also demonstrate a novel role for mTORC2 in the modulation of nuclear p27 levels
Michels et al., Mol Cell Biol 2010 : mTORC1 directly phosphorylates and regulates human MAF1 ... Our results describe molecular mechanisms by which mTORC1 controls human MAF1 , a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1
Lisse et al., FASEB J 2011 (Bone Neoplasms...) : DDIT4 , an inhibitor of mTOR signaling , is a direct target for 1,25 ( OH ) ( 2 ) D ( 3 ) and VDRE-BP, and functions to suppress cell proliferation in response to vitamin D
Liu et al., J Biol Chem 2012 (Diabetes Mellitus, Type 2...) : Brown adipose tissue insulin sensitivity and reduced adiposity of LRP6 ( +/- ) mice were accounted for by diminished Wnt dependent mTORC1 activity and enhanced expression of brown adipose tissue PGC1-a and UCP1
Sarbassov et al., Mol Cell 2006 : mTORC2 phosphorylates and activates Akt/PKB , a key regulator of cell survival ... mTORC2 phosphorylates and activates Akt/PKB , a key regulator of cell survival
Palaniappan et al., Mol Endocrinol 2012 : Furthermore, the pharmacological inhibition of mTORC1 or ribosomal protein S6 kinase 1 signaling prevented the LH/hCG induced phosphorylation of CREB
Cybulski et al., Proc Natl Acad Sci U S A 2009 (Fatty Liver) : mTORC2 , which consists of rictor, mSIN1, mLST8, and mTOR, is activated by insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB ... mTORC2 , which consists of rictor, mSIN1, mLST8, and mTOR, is activated by insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB
Melnik , World journal of diabetes 2012 : High consumption of leucine-rich proteins explains exaggerated mTORC1 dependent insulin secretion, increased ß-cell growth and ß-cell proliferation promoting an early onset of replicative ß-cell senescence with subsequent ß-cell apoptosis
Wang et al., J Immunol 2011 (Inflammation) : At the transcriptional level, mTORC1 inhibition reduced the DNA binding of CREB and this effect was reversed by GSK3 inhibition ... As a result, mTORC1 inhibition increased the levels of NF-?B p65 associated with CREB binding protein ... As a result, mTORC1 inhibition increased the levels of NF-?B p65 associated with CREB binding protein
Chen et al., J Invest Dermatol 2013 (Psoriasis) : mTORC2-PKBa/Akt1 Serine 473 Phosphorylation Axis Is Essential for Regulation of FOXP3 Stability by Chemokine CCL3 in Psoriasis
Chuluunbaatar et al., Genes Dev 2010 (Herpes Simplex) : Viruses producing methyl-7 ( m7 ) GTP capped mRNAs, like Herpes Simplex Virus-1 ( HSV-1 ), stimulate cap dependent translation by activating mTORC1 to inhibit the translational repressor 4E-binding protein 1 (4E-BP1)
Liu et al., Oncogene 2008 : Both S6K1 and 4E-BP1 pathways, mediated by the mTOR-raptor complex , are involved in the regulation of IGF-I stimulated F-actin reorganization, but only the former controls IGF-I stimulated phosphorylation of the focal adhesion proteins
Moschella et al., Cell Signal 2013 : Since mTORC2 is known to mediate the activation of a prosurvival kinase, Akt, we analyzed whether mTORC2 directly mediates Akt activation or whether it requires the participation of another prosurvival kinase, PKCe ( epsilon isoform of protein kinase-C )
DeYoung et al., Genes Dev 2008 (Breast Neoplasms) : Endogenous REDD1 is required for both dissociation of endogenous TSC2/14-3-3 and inhibition of mTORC1 in response to hypoxia ... REDD1 mutants that fail to bind 14-3-3 are defective in eliciting TSC2/14-3-3 dissociation and mTORC1 inhibition , while TSC2 mutants that do not bind 14-3-3 are inactive in hypoxia signaling to mTORC1 ... REDD1 mutants that fail to bind 14-3-3 are defective in eliciting TSC2/14-3-3 dissociation and mTORC1 inhibition , while TSC2 mutants that do not bind 14-3-3 are inactive in hypoxia signaling to mTORC1
Liu et al., Endocrinology 2012 : Overexpression of either SIK1 or SIK2 in 4B cells reduced nuclear TORC2 levels ( Western blot ) and inhibited forskolin stimulated CRH transcription ( luciferase assay )
Peña-Llopis et al., EMBO J 2011 (MAP Kinase Signaling System) : Regulation of TFEB and V-ATPases by mTORC1 ... mTORC1 regulates V-ATPase expression both in cells and in mice ... V-ATPase regulation by mTORC1 involves a transcription factor translocated in renal cancer, TFEB ... mTORC1 coordinately regulates TFEB phosphorylation and nuclear localization and in a manner dependent on both TFEB and V-ATPases, mTORC1 promotes endocytosis
Pracheil et al., Genetics 2012 : More importantly, characterization of lst8d bypass mutants reveals a role for protein phosphatase 2A (PP2A) in the regulation of TORC2 signaling
Zhang et al., PloS one 2009 : Loss of function of the TSC1-TSC2 complex results in constitutive mTORC1 signaling and, through mTORC1 dependent feedback mechanisms and loss of mTORC2 activity, leads to a concomitant block of Akt signaling to its other downstream targets ... Loss of function of the TSC1-TSC2 complex results in constitutive mTORC1 signaling and, through mTORC1 dependent feedback mechanisms and loss of mTORC2 activity, leads to a concomitant block of Akt signaling to its other downstream targets ... In examining the requirements for different Akt mediated phosphorylation sites on TSC2, we find that only TSC2 mutants lacking all five previously identified Akt sites fully block insulin stimulated mTORC1 signaling in reconstituted Tsc2 null cells, and this mutant also inhibits adipogenesis ... In examining the requirements for different Akt mediated phosphorylation sites on TSC2, we find that only TSC2 mutants lacking all five previously identified Akt sites fully block insulin stimulated mTORC1 signaling in reconstituted Tsc2 null cells, and this mutant also inhibits adipogenesis
Kim et al., Mol Cell 2013 (Breast Neoplasms...) : The TTT-RUVBL complex was necessary for the interaction between mTORC1 and Rag and formation of mTORC1 obligate dimers
Dey et al., PloS one 2012 (Hypertrophy) : Tuberin and PRAS40, two other Akt substrates, and endogenous inhibitors of mTORC1 , regulate mesangial cell hypertrophy
Hietakangas et al., BMC cancer 2008 (Breast Neoplasms...) : TOR complex 2 (TORC2) activates AKT by phosphorylating it on the ` hydrophobic motif ' site
Kelleher et al., Am J Physiol Endocrinol Metab 2013 : In conclusion, the results show an immobilization induced attenuation of mTORC1 signaling mediated by induction of REDD1/2 and defective p70S6K1 phosphorylation
Sancak et al., Cell 2010 (MAP Kinase Signaling System) : Thus, Rag-Ragulator mediated translocation of mTORC1 to lysosomal membranes is the key event in amino acid signaling to mTORC1
Salmond et al., J Allergy Clin Immunol 2012 (Pneumonia) : Our goal was to investigate a role for mammalian target of rapamycin (mTOR) signaling in the activation of T ( H ) 2 and ILC responses and the induction of airway inflammation by IL-33
Hong-Brown et al., Am J Physiol Cell Physiol 2012 : Rag GTPases and AMPK/TSC2/Rheb mediate the differential regulation of mTORC1 signaling in response to alcohol and leucine ... Rag GTPases and AMPK/TSC2/Rheb mediate the differential regulation of mTORC1 signaling in response to alcohol and leucine ... Rag GTPases and AMPK/TSC2/Rheb mediate the differential regulation of mTORC1 signaling in response to alcohol and leucine ... Overexpression of constitutively active ( ca ) RagA and caRagC increased mTORC1 activity, as determined by increased S6K1 phosphorylation
Suryawan et al., J Appl Physiol 2010 : The present study aimed to characterize in more detail the effects of the postprandial rise in INS and AA on the activation and abundance of mTORC1 regulators in muscle and how this is modified by development ... Our results suggest that the enhanced activation of mTORC1 in muscle of neonatal pigs is in part due to regulation by PRAS40, PLD1 , and the Rag GTPases ... Our results suggest that the enhanced activation of mTORC1 in muscle of neonatal pigs is in part due to regulation by PRAS40, PLD1 , and the Rag GTPases
Völkers et al., Proc Natl Acad Sci U S A 2013 (Cardiomegaly) : Mechanistic target of rapamycin complex 1 ( mTORC1 ), necessary for cellular growth, is regulated by intracellular signaling mediating inhibition of mTORC1 activation ... Inhibition of mTORC1 by PRAS40 preferentially promotes protective mTORC2 signaling in chronic diseased myocardium
Chong et al., Prog Neurobiol 2012 (Neurodegenerative Diseases) : mTOR signaling is dependent upon the mTORC1 and mTORC2 complexes that are composed of mTOR and several regulatory proteins including the tuberous sclerosis complex ( TSC1, hamartin/TSC2, tuberin )
Nascimento et al., Arch Physiol Biochem 2009 (Diabetes Mellitus, Type 2...) : The interaction of PRAS40 with the mTOR complex 1 (mTORC1) inhibits the activity of mTORC1
Liao et al., J Cell Sci 2010 : Chemotactic activation of Dictyostelium AGC-family kinases AKT and PKBR1 requires separate but coordinated functions of PDK1 and TORC2
Boulbés et al., Biochem Biophys Res Commun 2011 : Based on our study we suggest that the mTORC2 dependent phosphorylation of Akt on Ser-473 takes place on the surface of ER
Beharry et al., Proc Natl Acad Sci U S A 2011 : Here, we find that a novel Pim kinase inhibitor, SMI-4a, or Pim-1 siRNA blocked the rapamycin-sensitive mammalian target of rapamycin ( mTORC1 ) activity by stimulating the phosphorylation and thus activating the mTORC1 negative regulator AMP dependent protein kinase (AMPK)
Villanueva et al., Endocrinology 2009 : Leptin and feeding regulate the mammalian target of rapamycin complex 1 ( mTORC1 ) in the hypothalamus, and hypothalamic mTORC1 contributes to the control of feeding and energy balance ... To determine the mechanisms by which leptin modulates mTORC1 in specific hypothalamic neurons, we immunohistochemically assessed the mTORC1 dependent phosphorylation of ribosomal protein S6 (pS6) ... In contrast, fasting and leptin deficiency suppress VMH mTORC1 signaling ... Furthermore, ghrelin, which activates orexigenic ARC neurons, increased ARC mTORC1 activity and induced colocalized pS6- and c-Fos-IR
Ikenoue et al., Methods Enzymol 2009 : In turn, mTORC1 regulates the activity of the translational machinery by modulating S6 kinase ( S6K ) activity and eIF4E binding protein 1 ( 4E-BP1 ) through direct phosphorylation
Burgos et al., Horm Metab Res 2013 : The inhibitory effects of AMPK activation on mTORC1 signaling were associated with a marked increase in Ser792 phosphorylation on raptor