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AKT1 — TNF
Text-mined interactions from Literome
Ozes et al., Nature 1999
:
TNF activates phosphatidylinositol-3-OH kinase ( PI(3)K ) and its downstream target
Akt ( protein kinase B ) ... Thus, both
Akt and NIK are
necessary for
TNF activation of NF-kappaB
Roberts et al., Hepatology 2000
:
The
role of
protein kinase B and mitogen activated protein kinase in epidermal growth factor and
tumor necrosis factor alpha mediated rat hepatocyte survival and apoptosis
Hermann et al., Arterioscler Thromb Vasc Biol 2000
:
Furthermore, we investigated the
effect of
TNF-alpha on
Akt phosphorylation by Western blot analysis with the use of a phosphospecific Akt antibody
Madge et al., J Biol Chem 2000
:
Here we report that both
TNF and IL-1
activate the anti-apoptotic protein kinase
Akt in growth factor and serum deprived EC, assessed by Western blotting for phospho-Akt
Kitaura et al., J Exp Med 2000
:
Akt in turn can
regulate positively the transcriptional activity of interleukin (IL)-2 and tumor necrosis factor
(TNF)-alpha promoters ... Importantly,
Akt regulates the production and secretion of IL-2 and
TNF-alpha in FcepsilonRI stimulated mast cells
Rauch et al., FEBS Lett 2000
:
The present study investigates the
role of
Akt in the activation of NF-kappa B by
tumor necrosis factor-alpha ( TNF alpha, 10 ng/ml ) and PDGF-BB ( 20 ng/ml ) in human vascular smooth muscle cells ( SMC ), skin and foreskin fibroblasts
Tudan et al., J Immunol 2000
(MAP Kinase Signaling System) :
CPPD crystals were observed to
induce a robust and transient activation of ERK1, ERK2, and
Akt , whereas
TNF-alpha produced only a modest and delayed activation of Akt ... In the presence of TNF-alpha,
Akt activity was enhanced, and CPPD crystal induced activation of ERK1 and ERK2 was more sustained than with CPPD crystals alone, but
TNF-alpha itself
reduced the basal phosphotransferase activities of these MAP kinases
Hiraoka et al., Am J Physiol Heart Circ Physiol 2001
:
The
activation of phosphatidylinositol (PI) 3-kinase and
Akt/protein kinase B (PKB) by tumor necrosis factor
(TNF)-alpha and their roles on stimulation of protein synthesis were investigated in cultured neonatal rat cardiac myocytes ... The
activation of phosphatidylinositol (PI) 3-kinase and
Akt/protein kinase B (PKB) by tumor necrosis factor
(TNF)-alpha and their roles on stimulation of protein synthesis were investigated in cultured neonatal rat cardiac myocytes ...
TNF-alpha induced marked activation of PI3-kinase and
Akt/PKB , and the activation of PI3-kinase and Akt/PKB was rapid ( maximal at 10 and 15 min, respectively ) and concentration dependent ...
Akt/PKB activation by
TNF-alpha was inhibited by a PI3-kinase-specific inhibitor LY-294002 and adenovirus mediated expression of a dominant negative mutant of PI3-kinase, indicating that TNF-alpha activates Akt/PKB through PI3-kinase activation ...
Akt/PKB activation by
TNF-alpha was inhibited by a PI3-kinase-specific inhibitor LY-294002 and adenovirus mediated expression of a dominant negative mutant of PI3-kinase, indicating that TNF-alpha activates Akt/PKB through PI3-kinase activation
Ozes et al., Proc Natl Acad Sci U S A 2001
(Insulin Resistance) :
Conversely,
TNF inhibition of IRS-1 tyrosine phosphorylation was
blocked by kinase dead
Akt
Osawa et al., J Immunol 2001
:
TNF-alpha induced activations of PI3K and
Akt were inhibited by DMS
Zhang et al., Cell Death Differ 2001
(MAP Kinase Signaling System) :
In BAE cells,
TNF activates MAP kinase in a MAP kinase kinase 1 (MEK1) manner and
Akt in PI3-kinase dependent manner ... These results suggest that
TNF induced MAP kinase and
PI3-kinase/Akt signaling play important roles in protecting BAE cells from TNF cytotoxicity
Beresford et al., J Interferon Cytokine Res 2001
(Prostatic Neoplasms) :
Suppression of
PI3'-kinase/Akt signaling markedly
enhanced the apoptotic activity of both
TNF and TRAIL in LNCaP cells but not in PC-3 cells
Zhang et al., Arthritis Rheum 2001
(Arthritis, Rheumatoid...) :
The levels of phosphorylated
Akt and Akt kinase activity were
increased by stimulation of primary RASF with
TNFalpha ( 10 ng/ml )
Fang et al., Eur J Biochem 2001
(Carcinoma, Hepatocellular...) :
In
response to
TNF-alpha alone, FAK antisense cDNA transfectants showed a decrease in the level of
PKB
Goetze et al., Biochem Biophys Res Commun 2001
:
Insulin induced phosphorylation of
Akt downstream of PI3K was
inhibited by
TNFalpha in a similar pattern
O'toole et al., Biochem J 2001
:
Both
TNF-alpha and insulin-like growth factor 1 (IGF-1)
caused a 6-10-fold wortmannin-sensitive increase in
protein kinase B (PKB) activity within 5 min ... We conclude that, at physiological concentrations,
TNF-alpha activates endogenous
PKB by stimulating PDK2 ( increase in Ser ( 473 ) phosphorylation ) in a PI3-kinase dependent ( wortmannin-sensitive ) manner, without causing detectable stimulation of PDK1 ( no increase in Thr ( 308 ) phosphorylation ) or ARNO translocation
Kawanaka et al., Hepatology 2002
(Hypertension, Portal) :
In PHT gastric mucosa we studied ( 1 ) eNOS phosphorylation ( at serine 1177 ) required for its activation ; ( 2 ) association of the phosphatidylinositol 3-kinase ( PI 3-kinase ), and its downstream effector Akt, with eNOS ; and, ( 3 ) whether
TNF-alpha neutralization
affects eNOS phosphorylation and PI
3-kinase-Akt activation
Sandra et al., Cell Signal 2002
(Carcinoma, Squamous Cell...) :
In SAS cells,
TNF induced the phosphorylation of
Akt at both Ser473 and Thr308, causing the activation of Akt, and also induced the phosphorylation and degradation of IkappaB ( inhibitor of NFkappaB )
Kerby et al., Am J Physiol Lung Cell Mol Physiol 2002
(Cystic Fibrosis...) :
Strikingly, the
activation of p42 ( mapk/erk2 ) and
Akt by
TNF-alpha was also inhibited in the presence of NaCl
Shah et al., J Gastrointest Surg 2001
(Adenocarcinoma...) :
PI3K inhibition significantly enhanced the antiproliferative and proapoptotic effects of TNF-alpha in both cell lines, Ly294002 also blocked
TNF-alpha induced
Akt activation but failed to alter cytoplasmic IkappaBalpha degradation or subsequent NF-kappaB nuclear translocation
Kettritz et al., J Am Soc Nephrol 2002
:
The
effect of
TNF-alpha and MPO-ANCA on
Akt signaling was studied with immunoprecipitation and glutathione S-transferase pull-down assays ... p38 MAPK inhibition with 10 microM SB202190 that also decreased ANCA induced superoxide generation prevented S473 phosphorylation of
Akt in
response to
TNF-alpha and to ANCA ...
TNF-alpha stimulation
increased association of PAK1 with
Akt
Xagorari et al., Br J Pharmacol 2002
:
To determine the
role of
Akt in
TNF-alpha release, cells were transiently transfected with a dominant negative form of Akt ( K179M )
Jiang et al., J Biol Chem 2003
(Insulin Resistance) :
The results showed that both PMA and
TNFalpha inhibited insulin induced
Akt phosphorylation and promoted IRS1 phosphorylation on Ser-307 ... Salicylic acid pretreatment completely reversed the
effects of PMA and
TNFalpha on both
Akt and IRS1
Chong et al., Mol Pharmacol 2003
(Alzheimer Disease) :
Moreover, phosphatidylinositol
3-kinase/Akt signal was
required for excess
TNF-alpha production in human macrophages derived from THP-1 cells
Barsacchi et al., Mol Pharmacol 2003
:
Activation of endothelial nitric-oxide synthase by
tumor necrosis factor-alpha : a novel pathway
involving sequential activation of neutral sphingomyelinase, phosphatidylinositol-3 ' kinase, and
Akt
Osawa et al., J Immunol 2003
:
This proapoptotic action can be explained by its inhibitory findings on survival signals ; inhibition of
TNF-alpha induced activation and expression of phosphatidylinositol 3-kinase
(PI3K)/Akt , and also blockage of expression of Mcl-1, an antiapoptotic Bcl-2 family member which is located downstream of Akt, was inhibited by IEX-1S
Gao et al., J Biol Chem 2003
(Insulin Resistance) :
Phosphorylation of
Akt and the mammalian target of rapamycin ( but not extracellular regulated kinase or PKCzeta ) in
response to
TNF-alpha was inhibited by aspirin treatment
Pastorino et al., Am J Physiol Gastrointest Liver Physiol 2003
:
Additionally, ethanol exposed cells display a blunting of
TNF-alpha induced
Akt activation and Bcl-2 antagonist of cell death phosphorylation that may account, in part, for the increased sensitivity of the mitochondria to Bax mediated damage
Zhang et al., J Biol Chem 2003
:
Phosphorylation of VEGFR2 at Tyr-801 and Tyr-1175, the critical sites for VEGF induced PI3K-Akt signaling, was not involved in
TNF mediated
Akt activation
Kim et al., J Biol Chem 2004
:
Down-regulation of PTEN by NIK/NF-kappaB results in activation of the PI3K/Akt pathway and augmentation of
TNF-alpha induced
PI3K/Akt stimulation
Takada et al., J Biol Chem 2004
:
Furthermore, flavopiridol suppressed
TNF induced activation of
Akt
Asehnoune et al., J Immunol 2004
:
Antioxidant treatment of LPS stimulated neutrophils also inhibited the production of proinflammatory cytokines (
TNF-alpha , macrophage inflammatory protein-2, and IL-1beta ), as well as
activation of the kinases IkappaB kinase alpha, IkappaB kinase beta, p38,
Akt , and extracellular receptor activated kinases 1 and 2
Gupta et al., Biochim Biophys Acta 2004
:
The
effects of
tumor necrosis factor-alpha (TNF-alpha) on insulin induced phosphorylation of
protein kinase B-alpha (PKB-alpha) and downstream enzyme glycogen synthase kinase-3 beta ( GSK-3 beta ) was examined in HepG2 liver cells
Jhun et al., Biochem Biophys Res Commun 2004
:
5-Aminoimidazole-4-carboxamide riboside suppresses lipopolysaccharide
induced TNF-alpha production through inhibition of phosphatidylinositol
3-kinase/Akt activation in RAW 264.7 murine macrophages
Takada et al., J Biol Chem 2004
:
Most surprisingly,
TNF induced
Akt activation also required the presence of GSK-3beta
Shishodia et al., J Immunol 2004
(Carcinoma, Non-Small-Cell Lung...) :
Celecoxib also inhibited the
TNF induced interaction of
Akt with I kappa B alpha kinase (IKK)
Matsuyama et al., Biochem Biophys Res Commun 2004
:
Western blot analyses revealed that
Akt , which acts as a survival factor in cells, was activated in SMP30, but not mock, transfectants either in the
presence or absence of
TNF-alpha plus Act-D
Ha et al., Exp Cell Res 2004
:
In contrast, antioxidants did not prevent
TNF-alpha induced
Akt and NF-kappaB activation
Kamata et al., Int J Hematol 2004
:
Stimulation of human neutrophils with granulocyte colony stimulating factor ( G-CSF ), granulocyte-macrophage CSF (GM-CSF), or
tumor necrosis factor alpha (TNF) resulted in phosphorylation of
Akt , the potency being GM-CSF > G-CSF = TNF, which was inhibited by wortmannin
D'Alessio et al., Am J Pathol 2005
:
Methyl-beta-cyclodextrin did not alter total cell surface expression of TNFR1 or TNF induced degradation of IkappaBalpha, a measure of nuclear factor-kappaB activation, but it did inhibit
TNF induced phosphorylation of
Akt , a measure of phosphatidylinositol-3 kinase activation
Tanaka et al., Free Radic Biol Med 2005
:
Similarly, DEM and CDNB inhibited
TNF-alpha induced
Akt and eNOS phosphorylation, suggesting that thiol modification is involved in eNOS inductive pathways
Ueno et al., Br J Cancer 2005
(Carcinoma, Hepatocellular...) :
However, gefitinib inhibited the
TNF-alpha induced activation of MAPKs and
Akt
Prasad et al., J Neurochem 2005
:
It inhibits
tumor necrosis factor alpha (TNFalpha) induced PI3-kinase,
Akt and NF-kappaB activation in these cells
Yasui et al., Cancer Res 2005
(Multiple Myeloma) :
Finally, it down-regulates interleukin-6 induced phosphorylation of
Akt , signal transducers and activators of transcription 3, and p42/44 mitogen activated protein kinase ; insulin-like growth factor-I triggered Akt phosphorylation ; and
tumor necrosis factor alpha
induced IkappaBalpha and nuclear factor-kappaB p65 phosphorylation
Sandra et al., Oral Oncol 2006
(Ameloblastoma...) :
These results suggested that TNFalpha induced both cell survival and apoptosis pathways in ameloblastoma and potential of TNFalpha in inducing apoptosis can be improved by inhibiting
TNFalpha induced
Akt and p44/42 mitogen activated protein kinase ( MAPK ) cell survival pathways
Kobayashi et al., Exp Dermatol 2005
:
We show ( i ) UV induced up-regulation of TNF-alpha mRNA and protein expression in keratinocytes ; ( ii ) cells treated with KTI before UV irradiation showed a significantly lower accumulation of
TNF-alpha protein in a dose dependent manner and a reduced UV-induced up-regulation of TNF-alpha mRNA expression ; ( iii ) KTI inhibited the induction of TNF-alpha target molecules interleukin-1beta (IL-1beta) and IL-6 proteins ; ( iv ) UV irradiation transiently activated c-Jun N-terminal kinase (JNK) and Akt signaling but only weakly activated extracellular signal regulated kinase ( ERK ) and p38 ; ( v ) KTI specifically
inhibited UV-induced activation of ERK, JNK, and p38, but not
Akt ; ( vi ) treatment of cells with SP600125, a pharmacological inhibitor of JNK, predominantly suppressed UV-induced up-regulation of TNF-alpha expression ; and ( vii ) KTI did not enhance suppression of UV-induced JNK phosphorylation by SP600125
Higuchi et al., Am J Physiol Heart Circ Physiol 2006
:
Both basal and insulin stimulated
Akt phosphorylation were
reduced by almost 70 % by
TNF-alpha overexpression
Aggarwal et al., Mol Pharmacol 2006
(Neoplasm Metastasis) :
Curcumin also inhibited
TNF induced
Akt activation and its association with IKK
Shishodia et al., Cancer Res 2005
(Carcinoma, Small Cell...) :
4-HPR also inhibited
TNF induced
Akt activation linked with IKK activation
Huang et al., J Pharmacol Exp Ther 2006
:
Activation of MAPK and
Akt by anti-HER2/neu
ScFv-TNF-alpha inhibited the apoptosis of SKBR3 cells induced by actinomycin D. Remarkably, anti-HER2/neu ScFv-TNF-alpha facilitated the repair of injured epithelia
Ando et al., Clin Cancer Res 2005
(Carcinoma, Non-Small-Cell Lung...) :
However,
TNF-alpha induced
Akt phosphorylation and IkappaB degradation were observed much less often in PC-9/ZD2001 cells than in PC-9 cells or PC-9/ZD2001R cells
Adams et al., J Agric Food Chem 2006
(Inflammation) :
PJ also abolished
TNFalpha induced
AKT activation, needed for NFkappaB activity
Zhang et al., Vascul Pharmacol 2006
:
TNF-alpha significantly
increased extracellular signal related kinases ( ERK ) and
protein kinase B (PKB) activation and, which was blocked by notoginsenoside R1, PD098059, U0126 or wortmannin
Ahn et al., J Biol Chem 2006
:
Further, the deletion of NQO1 abolished
TNF induced c-Jun N-terminal kinase,
Akt , p38, and p44/p42 mitogen activated protein kinase activation
Wang et al., Biochem Biophys Res Commun 2006
(Insulin Resistance) :
On the other hand, addition of
TNF-alpha or IL-6 neutralizing antibodies to the supernatant of co-culture
recovered both IRS-2 phosphorylation and
Akt activation
Lu et al., J Biol Chem 2006
:
TNF caused a transient increase in
Akt phosphorylation at Ser473 in MCF-7 cells ... Overexpression of PKCepsilon in MCF-7 cells increased
TNF induced
Akt phosphorylation at Ser473 resulting in its activation ... Knockdown of DNA-PK by siRNA inhibited
TNF induced
Akt phosphorylation and the antiapoptotic effect of Akt and PKCepsilon
Nanua et al., Am J Respir Cell Mol Biol 2006
:
Quercetin also inhibited
TNF-alpha induced PI 3-kinase activity,
Akt phosphorylation, intracellular H ( 2 ) O ( 2 ) production, NF-kappaB transactivation, IL-8 promoter activity, and steady-state mRNA levels, consistent with the notion that quercetin inhibits chemokine expression by attenuating NF-kappaB transactivation via a PI 3-kinase/Akt dependent pathway
Jin et al., Am J Physiol Gastrointest Liver Physiol 2006
(MAP Kinase Signaling System) :
Inhibition of Rac1 does not modulate
TNF-alpha induced ERK1/2 and
Akt activation
Rickle et al., J Neurosci Res 2006
(Encephalitis...) :
TNFalpha together with PTEN inhibition
increased phosphorylation of Ser ( 473 )
Akt and Ser ( 9 ) GSK3beta
Lim et al., FEBS Lett 2006
:
CpG ODN induced the phosphorylation of Akt, and the inhibition of
Akt by LY294002
suppressed CpG ODN induced
TNF-alpha , TNFR-II, and MMP-9 expressions
Takada et al., Oncogene 2007
:
Genetic deletion of PKR abrogates
TNF induced activation of IkappaBalpha kinase, JNK,
Akt and cell proliferation but potentiates p44/p42 MAPK and p38 MAPK activation ...
TNF induced
Akt activation needed for IKK activation was also abolished by deletion of PKR
Takai et al., Horm Metab Res 2006
:
TNF-alpha induced the phosphorylation of
Akt depending upon time ... The phosphorylation of
Akt induced by
TNF-alpha was markedly attenuated by LY294002 and wortmannin, inhibitors of PI3-kinase ... PD98059, a specific inhibitor of MEK, had little effect on the
TNF-alpha induced phosphorylation of
Akt
Radeff-Huang et al., J Biol Chem 2007
(Brain Neoplasms...) :
In contrast,
TNF-alpha stimulated
Akt phosphorylation, which was also required for DNA synthesis, was attenuated by SphK inhibition or SphK1 knockdown by small interfering RNA ... Furthermore, cyclin D expression was increased by
TNF-alpha in a SphK- and
Akt dependent manner ... Additional studies demonstrated that
TNF-alpha effects on DNA synthesis, ERK, and
Akt phosphorylation are not mediated through cell surface Gi -coupled S1P receptors, because none of these responses were inhibited by pertussis toxin
Ghosh et al., Endocrinology 2007
(Insulin Resistance) :
Western blot analysis of L6 cell lysates demonstrated impaired insulin stimulated phosphorylation of
Akt , serine/arginine-rich protein 40, and glycogen synthase kinase 3beta in
response to
TNFalpha and the short chain C6 ceramide analog
Zhan et al., J Cell Sci 2007
(Mechanotransduction, Cellular) :
Disrupting
TNF-alpha signaling by TNF-alpha neutralizing antibody or knocking out TNF-alpha receptors
blocked stretch activation of p38, but not ERK1/2, JNK or
AKT
Wang et al., Biochem Biophys Res Commun 2007
(Melanoma...) :
Treatment of B16 cells with siRNA targeted to Akt1/2 resulted in TNFalpha suppression, indicating that
Akt plays an important role in regulation of
TNFalpha expression
Bieler et al., Oncogene 2007
:
Distinctive role of integrin mediated adhesion in
TNF induced
PKB/Akt and NF-kappaB activation and endothelial cell survival ... Distinctive role of integrin mediated adhesion in
TNF induced
PKB/Akt and NF-kappaB activation and endothelial cell survival ... Here we report that integrin ligation acts permissive for
TNF induced
protein kinase B ( PKB/Akt ) but not nuclear factor (NF)-kappaB activation ... Taken together, these observations reveal a novel permissive role for integrins in
TNF induced
PKB/Akt activation and prevention of TNF induced death distinct of NF-kappaB, and implicate the actin cytoskeleton in PKB/Akt mediated cell survival ... Taken together, these observations reveal a novel permissive role for integrins in
TNF induced
PKB/Akt activation and prevention of TNF induced death distinct of NF-kappaB, and implicate the actin cytoskeleton in PKB/Akt mediated cell survival
Smith et al., J Bone Joint Surg Am 2007
(Prosthesis Failure) :
Similarly, the
Akt inhibitor
reduced TNF-alpha production by 83 % in response to titanium particles with adherent endotoxin without increasing cytotoxicity
Sandur et al., Free Radic Biol Med 2007
:
Similarly, suppression of
TNF induced
AKT activation by curcumin was also abrogated by glutathione
Ahn et al., Cancer Res 2007
(Skin Neoplasms) :
Deletion of NQO2 also abolished
TNF induced c-Jun NH2-terminal kinase,
Akt , p38, and p44/p42 mitogen activated protein kinase activation
Plaisance et al., Am J Physiol Endocrinol Metab 2008
:
TNF-alpha activated two signaling cascades : 1 ) ERK1/2 and its target eIF4E and 2 )
Akt and its downstream effectors GSK-3, p70 ( S6K ), and 4E-BP1 ...
TNF-alpha induced phosphorylation of
Akt , and ERK1/2 was inhibited by an antibody against TNF-alpha receptor 1 (TNF-R1) ... LY-294002 completely abolished
TNF-alpha induced stimulation of PS as well as phosphorylation of
Akt and its downstream targets GSK-3, p70 ( S6K ), and 4E-BP1
Rajesh et al., Br J Pharmacol 2008
:
TNF-alpha triggered up to approximately 80 % increase ( depending on the method used ) in CB2 receptor mRNA and/or protein expression in HCASMCs, and
induced Ras, p38 MAPK, ERK 1/2, SAPK/JNK and
Akt activation, while increasing proliferation and migration
Shima et al., Am J Hypertens 2008
:
TNF-alpha induced phosphorylation of extracellular signal regulated kinase ( ERK ) and
Akt , but not p38 mitogen activated protein kinase ( MAPK ), was attenuated by nicardipine, cilnidipine, benidipine, efonidipine, and azelnidipine
Liu et al., J Endocrinol 2008
:
GLP-1 treatment also inhibited
TNF-alpha mediated induction of
Akt phosphorylation
Fakhrzadeh et al., Toxicol Appl Pharmacol 2008
(Pneumonia) :
TNFalpha signaling
involves PI-3-kinase
(PI3K)/protein kinase B (PKB) , and p44/42 MAP kinase (MAPK) which are important in NF-kappaB activation
Lee et al., Mol Pharmacol 2008
:
Moreover,
TNF-alpha induced
Akt and CaM kinase II phosphorylation via cascades through Src/EGFR/PI3K and PLC/calcium/CaM, respectively
Takada et al., Mol Pharmacol 2008
(Neoplasms) :
It is noteworthy that this flavone also suppressed
TNF induced activation of
Akt , a cell survival kinase, and expression of various antiapoptotic proteins, such as IAP-1, IAP-2, XIAP, Bcl-2, Bcl-xL, and TRAF-1 ... Flavopiridol suppresses
tumor necrosis factor induced
activation of activator protein-1, c-Jun N-terminal kinase, p38 mitogen activated protein kinase ( MAPK ), p44/p42 MAPK, and
Akt , inhibits expression of antiapoptotic gene products, and enhances apoptosis through cytochrome c release and caspase activation in human myeloid cells
Dan et al., J Immunol 2008
:
TNF , in most cells examined,
activates Akt to use IKKalpha to control mTOR activation ... In MCF7 cells,
TNF does not
activate Akt and requires IKKbeta to activate mTOR
Faurschou et al., Exp Dermatol 2008
:
TNF-alpha stimulates
Akt by a distinct aPKC dependent pathway in premalignant keratinocytes ... We have recently shown that
TNF-alpha induced
Akt activation may promote the early stages of skin cancer ... In this work, we demonstrate that in the premalignant keratinocyte cell line HaCaT,
TNF-alpha activates
Akt , ERK1/2 and p38 ... The specific peptide blocking the activity of the atypical protein kinase C ( aPKC ) species zeta and iota/lambda abrogated the
effects of
TNF-alpha on
Akt and ERK1/2 but increased the activation of p38 ... The
TNF-alpha dependent phosphorylation of
Akt-ERK1/2 was slightly decreased by NF kappaB inhibition and in the presence of p38 blockers
Zhou et al., American journal of physiology. Renal physiology 2008
(Endotoxemia...) :
TNF-alpha also
caused PI3-kinase/Akt activation, which was further increased by PDTC and prevented by the PI3-kinase inhibitor, LY294002
Moylan et al., Am J Physiol Cell Physiol 2008
:
We used TNF treated C2C12 myotubes to test the hypothesis that
AKT-Foxo1/3 signaling
mediates TNF regulation of atrogin mRNA ... TNF increases AKT phosphorylation ( +50 % ) and stimulation of
AKT with IGF does not
prevent TNF induction of atrogin mRNA
Huang et al., Cell Mol Immunol 2008
(Calcium Signaling) :
Treatment with Gab2 siRNA significantly decreased Gab2 expression, inhibited the FcepsilonRI mediated mast cell release of beta-hexosaminidase and histamine, reduced the production of IL-4 and
TNF-alpha and
inhibited the phosphorylation of
Akt , PKCdelta and p38 mitogen activated protein kinase ( MAPK )
Zhang et al., Invest Ophthalmol Vis Sci 2009
(Diabetes Mellitus, Experimental...) :
However,
TNF-alpha induced
Akt phosphorylation was blocked, and inhibiting Akt dramatically decreased CCL2 production
Yu et al., Vascul Pharmacol 2009
(MAP Kinase Signaling System) :
TNF-alpha stimulated the phosphorylation levels of p38 MAPK, JNK, ERK1/2 and
Akt in vascular endothelial cells
Ahmed et al., Arthritis Rheum 2009
(Arthritis, Rheumatoid...) :
Inhibition of Mcl-1 by EGCG triggered caspase 3 activity in RA synovial fibroblasts, which was mediated via down-regulation of the
TNFalpha induced
Akt and NF-kappaB pathways
Lacerda et al., Cardiovasc Res 2009
(Disease Models, Animal...) :
Western blot analysis did not demonstrate the
involvement of
Akt or Erk1/2 in
TNF-PostC , whereas STAT-3 phosphorylation was increased in both IPostC and TNF-PostC
Grzelkowska-Kowalczyk et al., Cell Mol Biol Lett 2010
:
The aim of this study was to compare the
effects of
TNF-alpha , IL-1beta and IFN-gamma on the activation of
protein kinase B (PKB) , p70 ( S6k ), mitogen activated protein kinase ( MAPK ) and p90 ( rsk ), and on IGF-I stimulated glucose uptake and protein synthesis in mouse C2C12 myotubes
Rivas et al., Breast Cancer Res Treat 2010
(Breast Neoplasms...) :
Moreover,
TNFalpha promoted ErbB-2/ErbB-3 heterocomplex formation,
Akt activation and NF-kappaB transcriptional activation
Fu et al., J Vet Med Sci 2009
(Inflammation) :
Vaspin did not inhibit the
TNF-alpha ( 20 min ) activation of JNK, p38 and NF-kappaB, but only slightly
inhibited Akt
Ghosh et al., Neurochem Int 2010
(Brain Neoplasms...) :
TNFalpha induced oxidative stress dependent
Akt signaling affects actin cytoskeletal organization in glioma cells ...
TNFalpha mediated increase in
Akt phosphorylation was dependent on oxidative stress as Akt phosphorylation was abrogated in the presence of ROS inhibitor and elevated in cells transfected with SOD-1 siRNA
Minamitani et al., Mol Cell Endocrinol 2010
:
Rapamycin enhanced the IL-6 synthesis and the phosphorylation of
Akt induced by
TNF-alpha also in human osteoblasts
Subramanyam et al., J Biol Chem 2010
:
Staurosporine,
tumor necrosis factor-alpha , or a Fas ligand
inhibited both RVI and hypertonicity induced
Akt activation in a manner sensitive to a scavenger for reactive oxygen species ( ROS )
Tseng et al., J Cell Physiol 2010
:
TNF-alpha increased the FAK, PI3K, and
Akt phosphorylation
Tsou et al., J Cell Biochem 2010
:
TNF-alpha also
increased the
Akt and mTOR phosphorylation
Xie et al., Clinical and vaccine immunology : CVI 2010
:
IL-6 and
TNF-alpha , but not IL-1beta,
inhibited Akt phosphorylation within 15 min of insulin stimulation, but only IL-6 was inhibitory 30 min after stimulation
Choi et al., Pain 2010
(Disease Models, Animal...) :
Peripheral inflammation induces
tumor necrosis factor dependent AMPA receptor trafficking and
Akt phosphorylation in spinal cord in addition to pain behavior ...
Akt and GluR1 phosphorylation, AMPA receptor trafficking and mechanical allodynia were all
TNF dependent
Moon et al., Exp Mol Med 2010
(Diabetes Mellitus, Experimental...) :
The
TNFalpha induced suppression of the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and
Akt in 3T3-L1 adipocytes was also reversed by SAM
Saito et al., American journal of physiology. Renal physiology 2010
:
TNF-alpha caused activation of NF-kappaB, MAP kinases, and
PI3K-Akt in podocytes, whereas blockade of these molecules did not affect inhibition of RAR by TNF-alpha
Lee et al., J Cell Physiol 2010
(MAP Kinase Signaling System) :
On the other hand,
TNF-alpha stimulated the phosphorylation of c-Src, EGFR,
Akt , JNK1/2, and c-Jun, which were inhibited by pretreatment with Gö6983 ... We also showed that
TNF-alpha induced
Akt translocation and the formation of an Akt/p65/p300 complex
Zhang et al., J Pathol 2010
(Colitis...) :
Our results showed that GDNF resulted in a significant reduction in enhanced permeability,
inhibited MPO activity, IL-1beta and
TNF-alpha expression, and increased ZO-1 and
Akt expression
Llacuna et al., Hepatology 2010
(Liver Diseases...) :
I/R
induced early hepatic protein kinase B (
AKT ) phosphorylation in WT mice but not in Gas6 ( -/- ) mice without significant changes in c-Jun N-terminal kinase phosphorylation or nuclear factor kappa B translocation, whereas hepatic interleukin-1ß (IL-1ß) and
tumor necrosis factor (TNF) messenger RNA levels were higher in Gas6 ( -/- ) mice versus WT mice
Moon et al., J Ethnopharmacol 2011
(MAP Kinase Signaling System) :
Three compounds all dose-dependently increased not only PPAR-? expression in EA.hy926 cells but inhibited
TNF-a induced phosphorylation of
Akt , extracellular-signal regulated kinase ( ERK ) and protein kinase C ( PKC ) with different specificity
Tian et al., Zhongguo Zhong Yao Za Zhi 2010
(Arthritis, Rheumatoid) :
Res inhibited
TNF-alpha induced phosphorylation of
Akt and BAD in RA FLS
Faurschou et al., Dan Med Bull 2010
:
TNF-a activated the protein kinase
B/Akt and regulation of its downstream targets, mTOR, Bad and FoxO3a
Sridharan et al., Cancer Res 2011
(Breast Neoplasms) :
In contrast to S6K1, depletion of S6K2 by siRNA decreased basal and
TNF induced
Akt phosphorylation
Wang et al., J Cell Mol Med 2012
(Carcinoma, Hepatocellular...) :
Tumour necrosis factor-a (TNF-a) significantly
induced phosphorylation of p38 MAPK, ERK,
Akt and production of IL-8 from HCC cells, which were prevented by SB203580 ( p38 MAPK inhibitor ), PD98059 ( ERK inhibitor ), LY294002 and Wortmannin ( PI3K inhibitor ) and SB328437 ( CCR3 inhibitor )
Lee et al., Int Immunopharmacol 2011
(Dermatitis, Atopic) :
3,4,5-Tricaffeoylquinic acid, Bay 11-7085, Akt inhibitor and N-acetylcysteine inhibited the
TNF-a induced activation of NF-?B, activation of
Akt , and formation of reactive oxygen and nitrogen species
Kim et al., J Pharmacol Exp Ther 2011
:
Furthermore, luteolin inhibited
TNF-a induced phosphorylation of mitogen activated protein kinase/extracellular signal regulated kinase ( ERK ) kinase 1/ERK/p90 ( RSK ), mitogen activated protein kinase kinase 4/c-Jun N-terminal kinase/c-Jun, and
Akt/p70 ( S6K )
Hwa et al., The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 2011
:
Genipin dose- and time-dependently increased PPAR-? expression and inhibited
TNF-a induced phosphorylation of
Akt and PKC with different degrees
Fong et al., J Ethnopharmacol 2011
(Cardiovascular Diseases) :
The molecular mechanism of the action may include the up-regulation of
IRS/AKT and JNK pathways as well as the
inhibition of
TNF and p38 pathways
Dhingra et al., PloS one 2011
:
Present study investigates the
role of
Akt and Jak/Stat pathway in the IL-10 modulation of
TNF-a induced cardiomyocyte apoptosis ... It is suggested that IL-10 modulation of
TNF-a induced cardiomyocyte apoptosis is
mediated by
Akt via Stat3 activation
Liu et al., Mol Biol Rep 2012
:
Blocking Erk or
Akt by pharmacological agent
reduced TNF-a or NO production in MMD overexpressing macrophages, respectively
Zhao et al., J Lipid Res 2012
:
Further studies showed that
TNF-a decreased expression of the antiapoptotic proteins Bcl-2 and Bcl-xL, decreased I?Ba and PPAR?, and also
inhibited PI3K dependent
Akt and EGFR signaling
Sheriff et al., Mol Cell Endocrinol 2012
(Burns...) :
DAG also reversed or attenuated the
TNF+IFN induced reduction in phosphorylation of
Akt , FOXO1, 4E-BP-1, and GSK-3ß in myotubes
Jude et al., Am J Respir Cell Mol Biol 2012
(Asthma) :
LY294002 and wortmannin inhibited
TNF-a induced
Akt activation, whereas only LY294002 inhibited CD38 expression
Oh et al., Toxicol In Vitro 2012
(Fatty Liver) :
Moreover, PA inhibited the
TNF-a induced phosphorylation of
AKT , but not c-Jun N-terminal kinase, indicating that inhibition of survival signaling pathways activated by TNF-a may explain the effects of PA on TNF-a induced cytotoxicity
Balwani et al., PloS one 2012
:
Thus, MPTAG mediated inhibition of
TNF-a induced
Akt activation was independent of PI-3K and dependent on PKA ... Most importantly, MPTAG restores the otherwise repressed activity of PKA and inhibits the
TNF-a induced
Akt phosphorylation at both Thr308 and Ser473 residues
Berasain et al., Dig Dis 2012
(Carcinoma, Hepatocellular...) :
AR was necessary for
TNF-a activation of ERK1/2 and
Akt signaling in hepatocytes
Wang et al., Cancer Res 2013
:
When combined with TNF-a, it suppresses
TNF-a activation of
AKT by inhibiting TNF-a induced tRXR-a interaction with the p85a regulatory subunit of PI3K ... CF31 inhibition of
TNF-a activation of
AKT also results in TNF-a dependent activation of caspase-8 and apoptosis
Lu et al., J Clin Immunol 2013
(Arthritis, Rheumatoid...) :
We found that MAPK and
Akt inhibitors, but not PI3K inhibitor, remarkably
suppressed ACPA mediated
TNF-a production
Zhang et al., Journal of molecular cell biology 2013
(Encephalomyelitis, Autoimmune, Experimental...) :
Interestingly, this regulatory pathway is iTreg cell specific as
TNF-a does not
activate Akt in naturally occurring regulatory T cells, therefore conferring a selective effect of TNF-a and its antagonism on iTreg cells
Tian et al., Rheumatol Int 2013
:
Immunofluorescence staining showed that
TNF-a alone
increased the production of
P-Akt , whereas LY294002 and 50 µM resveratrol suppressed the TNF-a stimulated expression of P-Akt
Yang et al., Biochem Pharmacol 2013
:
In addition,
TNF-a stimulated
Akt phosphorylation was inhibited by PP1, AG1478, AG1296, or LY294002
Lee et al., PloS one 2013
(Adenocarcinoma...) :
Consistent with its ability to induce apoptosis, a-tomatine reduced
TNF-a induced
activation of the pro-survival mediator
Akt and its inhibition of NF-?B activation was accompanied by significant reduction in the expression of NF-?B dependent anti-apoptotic ( c-IAP1, c-IAP2, Bcl-2, Bcl-xL, XIAP and survivin ) proteins
Chen et al., J Neurosci 2013
(MAP Kinase Signaling System) :
Here, we report that we find no evidence for a direct physical or functional interaction between PGRN and TNFRs. Using coimmunoprecipitation and surface plasmon resonance (SPR) we replicated the interaction between PGRN and sortilin and that between TNF and TNFRI/II, but not the interaction between PGRN and TNFRs. Recombinant PGRN or transfection of a cDNA encoding PGRN did not antagonize
TNF dependent NF?B,
Akt , and Erk1/2 pathway activation ; inflammatory gene expression ; or secretion of inflammatory factors in BV2 microglia and bone marrow derived macrophages ( BMDMs )
Tang et al., Zhonghua Xin Xue Guan Bing Za Zhi 2013
:
TNF-a also significantly
activated the phosphorylation of PTEN,
AKT and FOXO3a ( P < 0.05 )