Gene interactions and pathways from curated databases and text-mining

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MTOR — RPTOR

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) : Both Indo and Nim reduced mTOR signaling activity in CRC cells that differ in their COX-2 expression in vitro and in vivo ... Additionally, Indo and Nim could reduce the mTOR signaling activity after COX-2 silencing in CRC cells ... mTOR signaling is involved in Indo- and Nim mediated suppression of CRC growth via a COX-2 independent pathway
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
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
Han et al., Cell Signal 2008 (Tuberous Sclerosis) : Pam ( Protein associated with Myc ) functions as an E3 ubiquitin ligase and regulates TSC/mTOR signaling ... Our results provide novel evidence that Pam can function as an E3 Ub ligase toward tuberin and regulate mTOR signaling , suggesting that Pam can in turn regulate cell growth and proliferation as well as neuronal function through the TSC/mTOR pathway in mammalian cells
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
White et al., Mol Cell Endocrinol 2013 : Muscle AMPK and raptor phosphorylation, mTOR inhibitors , were not altered by low testosterone ... Acute Akt activation in C ( 2 ) C ( 12 ) myotubes is sensitive to a high concentration of testosterone, and low concentrations of testosterone can activate mTOR signaling independent of Akt
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
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
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
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
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 )
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
Ibrahim et al., Science 2013 (Disease Models, Animal...) : The reduced ICMT activity caused prelamin A mislocalization within the nucleus and triggered prelamin A-dependent activation of AKT-mammalian target of rapamycin (mTOR) signaling , which abolished the premature senescence of Zmpste24-deficient fibroblasts ... ICMT inhibition increased AKT-mTOR signaling and proliferation and delayed senescence in human HGPS fibroblasts but did not reduce the levels of misshapen nuclei in mouse and human cells
Zhou et al., Mol Biol Cell 2012 : We show that treatment with a combination of phorbol 12-myristate 13-acetate ( PMA ) plus ionophore A23187 ( Io ), which induces NFAT activation, increased REDD1 mRNA and protein expression and inhibited mTOR signaling ; pretreatment with the calcineurin inhibitor cyclosporin A ( CsA ), an antagonist of NFAT signaling, decreased REDD1 induction and mTOR inhibition ... We show that treatment with a combination of phorbol 12-myristate 13-acetate ( PMA ) plus ionophore A23187 ( Io ), which induces NFAT activation, increased REDD1 mRNA and protein expression and inhibited mTOR signaling ; pretreatment with the calcineurin inhibitor cyclosporin A ( CsA ), an antagonist of NFAT signaling, decreased REDD1 induction and mTOR inhibition
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
Liu et al., Communicative & integrative biology 2011 : Resveratrol inhibits mTOR signaling by targeting DEPTOR
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
Zhang et al., Basic Res Cardiol 2012 (Calcium Signaling...) : The aim of this study was to investigate the role of Na/K-ATPase/mTOR signaling in myocardial TNF-a expression during endotoxemia ... Inhibition of Na/K-ATPase activates Ca ( 2+ ) /CaMK/mTOR signaling , which promotes myocardial TNF-a protein production and cardiac dysfunction during endotoxemia
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 ... Our results demonstrate that resveratrol profoundly inhibits ERK and mTOR signaling in sensory neurons in a time- and concentration dependent fashion and that these effects are mediated by AMPK activation and independent of sirtuin activity
Tong et al., Mol Carcinog 2012 : Although AMPK is traditionally thought to play a major role in the regulation of cellular lipid and protein metabolism, recent discoveries reveal that AMPK inhibits mammalian target of rapamycin (mTOR) signaling and connects with several tumor suppressors such as liver kinase B1 (LKB1), p53, and tuberous sclerosis complex 2 (TSC2), indicating that AMPK may be a potential target for cancer prevention and treatment ... Apigenin induced AMPK activation inhibited mTOR signaling and further induced autophagy in human keratinocytes
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
Zannella et al., Radiother Oncol 2011 (Colorectal Neoplasms) : These data reveal novel functional roles for AMPK in regulating mTOR signaling , cell cycle, survival and metabolic responses to IR
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
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
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
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
Yang et al., Hepatology 2009 (Liver Neoplasms) : Consistent with this notion, enhanced expression of VEGF-A and activation of Akt/mTOR signaling , comparable to the levels of paired HCC tissues, were also detected in HBV related nontumorous livers
You et al., PloS one 2012 (MAP Kinase Signaling System...) : Hence, we reasoned that a mechanically induced increase in PA might promote mTOR signaling via an ERK dependent mechanism
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
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 )
Kim et al., J Cell Biochem 2012 : Erythropoietin mediated bone formation is regulated by mTOR signaling
Ma et al., Mol Cell Biol 2006 (Breast Neoplasms...) : In support of this mechanism, reduction of Irs-2 expression in Irs1 ( -/- ) tumor cells restored mTor signaling to wild-type levels
Zhao et al., Anat Rec (Hoboken) 2011 (Nasopharyngeal Neoplasms) : AMPK mediated inhibition of mTORC1 signaling may be involved in this process
Kim et al., Cell 2002 : The association of raptor with mTOR also negatively regulates the mTOR kinase activity
Hara et al., Cell 2002 : The binding of raptor to mTOR is necessary for the mTOR catalyzed phosphorylation of 4EBP1 in vitro, and it strongly enhances the mTOR kinase activity toward p70alpha
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
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...) : 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
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
Liu et al., J Biol Chem 2010 : Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR ... Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR ... 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
Kam et al., FASEB J 2004 : The reduction in PLD activity in both situations impaired the effect of LPA on mTOR signaling but did not inhibit the effect of PDGF ... The reduction in PLD activity in both situations impaired the effect of LPA on mTOR signaling but did not inhibit the effect of PDGF
Cipriano et al., J Clin Invest 2012 (Cell Transformation, Neoplastic...) : Binding of FAM83B with CRAF disrupted CRAF/14-3-3 interactions and increased CRAF membrane localization, resulting in elevated MAPK and mammalian target of rapamycin (mTOR) signaling
Southgate et al., J Biol Chem 2007 : FOXO1 regulates the expression of 4E-BP1 and inhibits mTOR signaling in mammalian skeletal muscle ... FOXO1 regulates the expression of 4E-BP1 and inhibits mTOR signaling in mammalian skeletal muscle ... Using C2C12 mouse myoblasts that stably express inducible FOXO1-ER fusion proteins and transgenic mice that specifically overexpress constitutively active FOXO1 in skeletal muscle ( FOXO ( ++/+ ) ), we show that FOXO1 inhibits mTOR signaling and protein synthesis
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
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
Kramer et al., J Appl Physiol 2011 (Airway Remodeling...) : Thus rapamycin reduced airway remodeling and AHR, demonstrating an important role for mTOR signaling in TGF-a-induced/EGF receptor mediated reactive airway disease
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 : Melanocortin-4 receptor activation promotes insulin stimulated mTOR signaling ... 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
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
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
Banerjee et al., Cancer Res 2010 : The NF1 gene product neurofibromin negatively regulates Ras and mammalian target of rapamycin (mTOR) signaling , prompting clinical trials to evaluate the ability of Ras and mTOR pathway inhibitors to arrest NF1 associated tumor growth
Winbanks et al., J Cell Biol 2012 (Hypertrophy) : Furthermore, we identify Smad3 as the critical intracellular link that mediates the effects of follistatin on mTOR signaling ... Importantly, the regulation of Smad3- and mTOR dependent events by follistatin occurred independently of overexpression or knockout of myostatin, a key repressor of muscle development that can regulate Smad3 and mTOR signaling and that is itself inhibited by follistatin
Sherbakova et al., Mol Biol (Mosk) 2008 (Prostatic Neoplasms) : Transfection of PTEN into PTEN-deficient PC3 as well as rapamycin treatment caused the inhibition of PI3K/Akt/mTOR signaling and resulted in cell sensitization to the action of doxorubicin and vinblastine
Schewe et al., Proc Natl Acad Sci U S A 2008 (Carcinoma, Squamous Cell...) : Downstream, ATF6alpha induces survival through the up-regulation of Rheb and activation of mTOR signaling independent of Akt ... Downstream, ATF6alpha induces survival through the up-regulation of Rheb and activation of mTOR signaling independent of Akt
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
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
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
Niziolek et al., J Cell Physiol 2009 (Body Weight...) : We investigated whether the bone building effects of intermittent PTH require functional mTOR signaling
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
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
Pantovic et al., Bone 2013 : AMPK knockdown prevented early mTOR inhibition and autophagy induction, as well as late activation of Akt/mTOR signaling , while Akt inhibition suppressed mTOR activation without affecting AMPK phosphorylation
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
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
Browne et al., Mol Cell Biol 2004 : eEF2 kinase is thus a target for mTOR signaling independently of previously known downstream components of the pathway
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
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
Delgoffe et al., Mol Immunol 2009 : Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation ... Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation
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
Martin et al., Biol Reprod 2003 : The resultant mTOR signaling could trigger polyamine, insulin-like growth factor II , and nitric oxide production in blastocysts and the increased cell motility sometimes associated with synthesis of these bioactive molecules
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
Oddo , Front Biosci (Schol Ed) 2012 (Alzheimer Disease) : The role of mTOR signaling in Alzheimer disease
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
He et al., Ann Oncol 2012 (Breast Neoplasms...) : Human epidermal growth factor receptor ( HER2 ), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling , and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer ... Human epidermal growth factor receptor ( HER2 ), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling , and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer ... Human epidermal growth factor receptor ( HER2 ), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling , and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer ... Human epidermal growth factor receptor ( HER2 ), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling , and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer
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
Dong et al., Acta Pharmacol Sin 2013 (Carcinoma, Non-Small-Cell Lung...) : To investigate the role of LKB1 in regulation of mTOR signaling in non-small cell lung cancer ( NSCLC ) cells
Shimizu et al., Peptides 2010 : The mammalian target of rapamycin (mTOR) has been implicated in the regulation of physiological functions such as cell growth and proliferation, and glucocorticoids reportedly inhibit mTOR signaling in peripheral tissues ... In this study, we examined whether the mTOR signaling in the hypothalamus is involved in the regulation of neuropeptide Y (Npy) gene expression in the arcuate nucleus by glucocorticoids
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
Chen et al., Lab Invest 2010 : N-acetyl-L-cysteine (NAC) , a scavenger of reactive oxygen species ( ROS ), blocked H ( 2 ) O ( 2 ) inhibition of mTOR signaling
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
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
Das et al., Cell Signal 2008 : shRNA mediated downregulation of raptor inhibited TGFbeta stimulated mTOR kinase activity, resulting in inhibition of phosphorylation of S6 kinase and 4EBP-1
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
Hernández-Negrete et al., J Biol Chem 2007 : Rapamycin, a widely used inhibitor of mTOR signaling , did not inhibit Rac activity and cell migration induced by leucine, indicating that P-Rex1, which we found associated to both mTOR complexes, is only active when in the mTORC2 complex
Briz et al., J Neurosci 2013 : Our results reveal a critical role for calpain-2 in BDNF induced mTOR signaling and dendritic protein synthesis via PTEN, hamartin, and tuberin degradation ... Our results reveal a critical role for calpain-2 in BDNF induced mTOR signaling and dendritic protein synthesis via PTEN, hamartin, and tuberin degradation
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
Nagaraja et al., Mol Endocrinol 2010 (Adenocarcinoma, Clear Cell...) : Overexpression of mir-100 inhibited mTOR signaling and enhanced sensitivity to the rapamycin analog RAD001 ( everolimus ), confirming the key relationship between mir-100 and the mTOR pathway
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
Ham et al., Exp Cell Res 2013 (Cardiomegaly...) : TRIM72 specifically regulated IGF-1 dependent AKT-mTOR signaling , resulting in a reduction of the size of cardiomyocytes ... TRIM72 specifically regulated IGF-1 dependent AKT-mTOR signaling , resulting in a reduction of the size of cardiomyocytes
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
Tzatsos et al., Mol Cell Biol 2006 (Diabetes Mellitus, Type 2) : Here, we demonstrate that nutrients suppress phosphatidylinositol 3 (PI3)-kinase/Akt signaling via Raptor dependent mTOR ( mammalian target of rapamycin ) -mediated phosphorylation of insulin receptor substrate 1 (IRS-1)
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
Zhao et al., Cancer Res 2013 : The mTOR positively regulates cell proliferation and survival through forming 2 complexes with raptor ( mTOR complex 1 ; mTORC1 ) or rictor ( mTOR complex 2 ; mTORC2 )
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)
Vojtechová et al., Neoplasia (New York, N.Y.) 2008 : Regulation of mTORC1 signaling by Src kinase activity is Akt1 independent in RSV transformed cells
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
Castillo-Pichardo et al., Nutr Cancer 2012 (Breast Neoplasms) : RQC was found to reduce Akt activity, induce the activation of AMPK, and inhibit mTOR signaling in breast cancer cells ... RQC was found to reduce Akt activity, induce the activation of AMPK , and inhibit mTOR signaling in breast cancer cells
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
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
Jaafar et al., Cell communication and signaling : CCS 2013 (Muscular Atrophy) : It is established that Phospholipase D ( PLD ) activates mTOR signaling , through the binding of its product phosphatidic acid ( PA ) to mTOR protein ... These observations suggest that PLD1 acts through the activation of both mTORC1 and mTORC2 to induce positive trophic effects on muscle cells
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
Kimball , Med Sci Sports Exerc 2006 : The focus of the present review is to briefly summarize current knowledge concerning the regulation of mTOR signaling by AMPK
Miyazaki et al., Am J Physiol Cell Physiol 2009 : REDD2 is enriched in skeletal muscle and inhibits mTOR signaling in response to leucine and stretch ... Overexpression of REDD2 in muscle cells significantly inhibited basal mTOR signaling and diminished the response of mTOR to leucine addition or mechanical stretch ... However, we found that REDD2 forms a complex with 14-3-3 protein and that increasing expression of REDD2 acts to competitively dissociate TSC2 from 14-3-3 and inhibits mTOR signaling
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
Liu et al., Mol Cancer Ther 2012 (Lung Neoplasms) : Inhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal regulated kinase 1 or 2 ( ERK1/2 ) and Akt in various types of cancer cells, which contributes to rapamycin resistance ... Inhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal regulated kinase 1 or 2 ( ERK1/2 ) and Akt in various types of cancer cells, which contributes to rapamycin resistance
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 ... Therefore, our findings indicate that mTOR mediated raptor phosphorylation plays an important role on activation of mTORC1
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
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
Williamson et al., Am J Physiol Endocrinol Metab 2006 (MAP Kinase Signaling System) : Overall, the data support the conclusion that AICAR induced AMPK activation suppresses protein synthesis through concurrent repression of mTOR signaling and activation of MAPK signaling, the combination of which modulates transient changes in the initiation and elongation phases of mRNA translation
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
Cunningham et al., Nature 2007 : Moreover, mTOR and raptor interacted with YY1, and inhibition of mTOR resulted in a failure of YY1 to interact with and be coactivated by PGC-1alpha
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
Tsai et al., Cell death & disease 2013 (Carcinoma, Squamous Cell...) : When WWOX was knocked down in SCC-15, MTX induced mTOR signaling and autophagy inhibition were blocked
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 ... These results demonstrate that SIRT1 negatively regulates mTOR signaling potentially through the TSC1/2 complex
Ha et al., Cardiovasc Res 2005 (Cardiomegaly...) : Our results demonstrate that TLR4 is a novel receptor contributing to the development of cardiac hypertrophy in vivo and that both the TLR4 mediated pathway and PI3K/Akt/mTOR signaling are involved in the development of cardiac hypertrophy in vivo
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
Xie et al., Cancer cell international 2013 : Klotho is a tumor suppressor in gastric cancer, which regulates IGF-1R phosphorylation and the subsequent activation of IRS-1/PI3K/Akt/mTOR signaling , tumor cell proliferation, apoptosis, and autophagy
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 : 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
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
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
Choi et al., J Biol Chem 2012 (Cardiomyopathies...) : In both primary tissue and cell culture models, overexpression of Dusp4 positively regulates AKT-mTOR signaling , resulting in impaired autophagy
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
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
Hornberger et al., Proc Natl Acad Sci U S A 2006 : The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle ... Finally, pharmacological inhibition of PLD blocked the mechanically induced increase in PA and the activation of mTOR signaling
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
Hofmann et al., Mol Biol Cell 2012 : In addition, cold shock leads to reduced mitochondrial function, energy depletion, concomitant activation of AMP activated protein kinase (AMPK) , and inhibition of mTOR signaling
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
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
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
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
Gupta et al., Blood 2012 (Lymphoma) : 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
Coiffier et al., Leukemia & lymphoma 2009 (Hematologic Neoplasms...) : Mantle cell lymphoma ( MCL ) was the first hematologic malignancy in which mTOR inhibition was explored as a treatment strategy, owing to its characteristic overexpression of cyclin D1, a G1 cyclin regulated by mTOR signaling
Villa-Cuesta et al., PloS one 2011 (Carcinoma, Hepatocellular...) : The effects on mTOR signaling were independent of effects on AMP activated kinase or 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
Jin et al., PloS one 2013 : We further demonstrated that miR-99 family members regulate cell proliferation, cell migration, and AKT/mTOR signaling ... Combined experimental and bioinformatics analyses revealed that miR-99 family members regulate AKT/mTOR signaling by targeting multiple genes, including known target genes ( e.g., IGF1R, mTOR ) and a new target ( AKT1 )
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
Zhan et al., Mol Cell Biol 2007 : Activation of apoptosis signal regulating kinase 1 ( ASK1 ) induced by inhibition of mTOR signaling leads to sustained phospho-c-Jun that is suppressed in cells with functional p53 or by forced expression of p21 ( Cip1 )
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
Zeng et al., Cell Signal 2008 (Neuroblastoma) : Roles of autophagy and mTOR signaling in neuronal differentiation of mouse neuroblastoma cells
Gan et al., J Biol Chem 2006 : Together, these results suggest that FAK might regulate S6K activation and cell size through its interaction with and phosphorylation of TSC2 and also provide a previously unappreciated role of TSC2 in the regulation of mTOR signaling by cell adhesion
Wang et al., Cancer Res 2012 (Disease Models, Animal...) : Here we describe a new genetically engineered mouse model of prostate cancer in which PI3K-Akt-mTOR signaling is activated by inducible disruption of PTEN , and extracellular signal regulated kinase 1/2 ( ERK1/2 ) MAPK signaling is activated by inducible expression of a BRAF ( V600E ) oncogene
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
Ciechomska et al., Oncogene 2013 (Brain Neoplasms...) : Decrease of phosphorylation of 4E-BP1, p70S6K1 and its downstream target S6 ribosomal protein demonstrate inhibition of mTOR signaling by CsA ... Decrease of phosphorylation of 4E-BP1 , p70S6K1 and its downstream target S6 ribosomal protein demonstrate inhibition of mTOR signaling by CsA ... Decrease of phosphorylation of 4E-BP1, p70S6K1 and its downstream target S6 ribosomal protein demonstrate inhibition of mTOR signaling by CsA
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
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
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
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
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
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
Albert et al., Mol Cancer Ther 2006 (Breast Neoplasms) : Irradiation induced Akt and mTOR signaling , and this signaling is attenuated by RAD001
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 ) )
Kwan et al., PloS one 2013 (Uterine Cervical Neoplasms) : Besides, impaired mTOR signaling activity also reduced DVL3 expression
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
Hegedus et al., Cancer Res 2008 (Disease Models, Animal...) : Because neurofibromin negatively regulates mammalian target of rapamycin (mTOR) signaling , we showed that pharmacologic mTOR inhibition in vivo led to decreased tumor cell proliferation in a dose dependent fashion associated with a decrease in tumor volume
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
Pan et al., Cell cycle (Georgetown, Tex.) 2012 (Precursor Cell Lymphoblastic Leukemia-Lymphoma) : Human insulin and analogs activated AKT/mTOR signaling and stimulated ALL cell proliferation ( as measured by flow cytometric methods ), but metformin and rosiglitazone blocked AKT/mTOR signaling and inhibited proliferation
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
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
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
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
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
Drakos et al., Leukemia 2009 (Lymphoma, Mantle-Cell) : As mTOR signaling is activated in MCL and may control cyclin D1 levels, we show that p53 activation may downregulate the AKT/mTOR pathway through a mechanism involving AMP kinase (AMPK)
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
Sancak et al., Science 2008 : Conversely, expression of a guanosine diphosphate bound Rag mutant prevented stimulation of mTORC1 by amino acids
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 ... 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 ... 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
Shen et al., Proc Natl Acad Sci U S A 2013 (Sarcoma) : microRNA-18a and microRNA-421, both of which target ATM, are positively controlled by mTOR signaling ... microRNA-18a and microRNA-421 , both of which target ATM, are positively controlled by mTOR signaling
Donahue et al., Eur J Immunol 2007 : In contrast, LPS induced mTOR signaling is strikingly resistant to wortmannin in both subsets
Goodman et al., Mol Biol Cell 2010 (Hypertrophy) : In this study, we determined that, in skeletal muscle, overexpression of Rheb stimulates a PI3K/PKB independent activation of mTOR signaling , and this is sufficient for the induction of a rapamycin-sensitive hypertrophic response
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
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
Liu et al., Eur J Pharmacol 2012 (Arthritis, Experimental) : To investigate the role of PI3K/Akt/mTOR signaling mediated by B cell activating factor belonging to the TNF family ( BAFF ) involved in anti-apoptosis of B lymphocytes in rats with collagen induced arthritis ( CIA ) and the regulation of epigallo-catechin-3-gallate ( EGCG )
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 ... RSK1 phosphorylation of Ser-1798 inhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mTOR signaling to S6K1
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 ... 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
Csibi et al., PloS one 2010 : The translation regulatory subunit eIF3f controls the kinase dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse
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
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
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
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 : The molecular basis for the differential effect of mTOR signaling on Akt is poorly understood ... 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
Kuang et al., Biochem Biophys Res Commun 2009 (Lymphoma...) : Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes ... Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes
Wang et al., Lipids in health and disease 2012 (Obesity) : HDL and apoA-I could activate PI3K-Akt-mTORC1 signaling which negatively regulates autophagy
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
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
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
Mabuchi et al., Cancer Res 2007 (Disease Models, Animal...) : In vivo effects of RAD001 on Akt-mTOR signaling , tumor cell proliferation, and blood vessel area were analyzed by immunohistochemistry and Western blot analysis
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 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
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
Huang et al., Cancer Lett 2009 (Carcinoma...) : Also, we found blockage mTORC1 inhibited Cyclin D1 expression in CNE-2 cells and enhanced cell apoptosis
Liu et al., Nephrol Dial Transplant 2012 (Hyperglycemia...) : PTEN/Akt/mTOR signaling stimulated by high concentration of glucose is regulated by Cx43 overexpression, which unveils part of the molecular mechanism of Cx43 in regulating hyperglycemia induced hypertrophy
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
Zhu et al., Circulation 2009 (Acute Disease...) : These data suggest that doxorubicin treatment induces acute cardiac dysfunction and reduces cardiac mass via p53 dependent inhibition of mTOR signaling and that loss of myocardial mass, and not cardiomyocyte apoptosis, is the major contributor to acute doxorubicin cardiotoxicity
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
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
She et al., Am J Physiol Endocrinol Metab 2011 (Body Weight...) : Thus, mutant huntingtin in skeletal muscle results in increased protein synthesis and mTOR signaling , which is countered by activation of the apoptotic and autophagic pathways, contributing to an overall catabolic phenotype and the severe muscle wasting
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
Julien et al., Mol Cell Biol 2010 : 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 )
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
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
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 : We hypothesized that AMPK mediated inhibitory effects on mTOR signaling depend on catalytic alpha2 and regulatory gamma3 subunits ... However, in WT mice, preincubation with AICAR completely inhibited insulin induced phosphorylation of mTOR targets, suggesting mTOR signaling is blocked by prior AMPK activation
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
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
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 ... We have studied whether Rheb is sufficient to activate mTOR signaling and promote protein synthesis and cardiac hypertrophy in adult rat ventricular cardiomyocytes ( ARVC ) ... 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
Roos et al., Am J Physiol Cell Physiol 2009 : We hypothesized that glucose, insulin, and IGF-I regulate placental amino acid transporters by inducing changes in mTOR signaling
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
Darido et al., Cancer Cell 2011 (Carcinoma, Squamous Cell...) : Deletion of Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of PI3K/AKT/mTOR signaling
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
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
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) : 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
Brown et al., Ann Clin Lab Sci 2006 (Neoplasms, Squamous Cell...) : Because the mammalian target of the rapamycin (mTOR) pathway contributes to the activation of NF-kappaB through immunophilin/mTOR signaling , we investigated : ( a ) the immunohistochemical expression and state of activation and potential clinical significance of components of the mTOR signal transduction pathway in SCCT patients ( morphoproteomics ) ; and ( b ) the inhibitory effects of rapamycin on the growth and state of activation of mTOR in 2 HNSCC cell lines ( pharmacoproteomics )
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
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
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
Dere et al., PloS one 2010 (Polycystic Kidney, Autosomal Dominant) : Interestingly, while membrane tethering of CP1 was required to activate TSC2 and repress mTOR, the ability of CP1 to inhibit mTOR signaling did not require primary cilia and was independent of AMPK activation
Du et al., J Anim Sci 2007 : Applying 5-aminoimidazole-4-carbox-amide 1-beta-d-ribonucleoside, an activator of AMPK, abolished the stimulation of mTOR signaling by leucine, showing that AMPK negatively controls mTOR signaling ... To further show the role of AMPK in mTOR signaling , myoblasts expressing a dominant negative AMPKalpha subunit were employed
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
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
Gan et al., Cancer Cell 2010 (Carcinoma, Renal Cell...) : mTORC1 is a validated therapeutic target for renal cell carcinoma (RCC)
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
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
Hegner et al., Arterioscler Thromb Vasc Biol 2009 : We studied effects of PI3K/Akt/mTOR signaling on phenotypic modulation of MSC and VSMC marker expression, including L-type Ca ( 2+ ) channels
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...) : Among these was the gene for DNA-damage-inducible transcript 4 ( DDIT4 ), an inhibitor of mammalian target of rapamycin (mTOR) signaling ... 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
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
Matsumoto et al., Cancer Res 2009 (Colorectal Neoplasms...) : Here, we found that the inhibition of mTOR signaling up-regulated CD133 expression at both the mRNA and protein levels in a CD133 overexpressing cancer cell line
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
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
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
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
Ji et al., Mol Pharmacol 2010 : Stimulation of endogenous EP1 receptors in human HepG2 hepatocellular carcinoma cells recapitulated the normoxic up-regulation of HIF-1 alpha observed in HEK cells, was sensitive to pertussis toxin, and involved the activation of mTOR signaling and phosphorylation of rpS6
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
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
Chen et al., Cell Signal 2013 : Further, after plumbagin treatment, activated AMPK directly phosphorylates Raptor to inhibit mTOR complex 1 (mTORC1) activation and Bcl-2 expression in colon cancer cells
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
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