Gene interactions and pathways from curated databases and text-mining

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Text-mined interactions from Literome

Yano et al., Proc Natl Acad Sci U S A 2008 (Bone Neoplasms...) : Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src dependent Akt activation
Slomiany et al., Inflammopharmacology 2008 : Our findings demonstrate that leptin protection of salivary gland acinar cells against ethanol cytotoxicity involves Src kinase mediated parallel activation of MAPK/ERK and Akt that result in up-regulation of the respective prostaglandin and nitric oxide synthase pathways
Matsui et al., Circulation 2007 (Ischemia) : PI3-kinase is associated with vascular endothelial growth factor induced PYK2/Src complex, and inhibition of Src blocked Akt activation
Hakak et al., Oncogene 2000 : Shp-2 mediates v-Src induced morphological changes and activation of the anti-apoptotic protein kinase Akt ... Shp-2 deficiency also reduced v-Src induced activation of the anti-apoptotic protein kinase Akt
Meng et al., Br J Cancer 2009 (Adenocarcinoma...) : In addition, the Src inhibitor, PP2, blocked the phosphorylation of FAK, ERK1/2, PI3K, and Akt
Winograd-Katz et al., Oncogene 2006 : In this study, we report that Cisplatin activates PKB/Akt in several cancer cell lines and that this activation is mediated by EGFR, Src and PI3-kinase
Sumitomo et al., Cancer Res 2001 (Prostatic Neoplasms) : Incubation of TSU-Pr1 cells with specific kinase inhibitors together with ET-1 or bombesin showed that IGF-IR activation is required for neuropeptide induced Akt phosphorylation, and that neuropeptide induced Akt activation is predominantly mediated by Src and phosphatidylinositol 3-kinase but not by mitogen activated protein kinase or protein kinase C
Chen et al., Cell Biol Int 2012 : In addition, the Src tyrosine kinase inhibitor, PP2, blocked ISO mediated both Akt and ERK activation and heavily suppressed viability
Lopez et al., J Biol Chem 2003 : TEL-M1 delocalization requires the kinase activity of v-SRC and is not induced by oncogenic RAS or AKT
Liu et al., Cancer Res 1998 (Ovarian Neoplasms) : Moreover, the activated Ras and v-Src , two proteins that transduce growth factor generated signals, also activated AKT2 , and this activation was not significantly enhanced by growth factor stimulation but was abrogated by wortmannin ... These results indicate that AKT2 is a downstream target of PI 3-kinase and that Ras and Src function upstream of PI 3-kinase and mediate the activation of AKT2 by growth factors
Vojtechová et al., Neoplasia (New York, N.Y.) 2008 : Disruption of the Src kinase activity results in substantial reduction of the phosphorylation and activity of the Akt/protein kinase B (PKB), phosphorylation of tuberin ( TSC2 ), mammalian target of rapamycin (mTOR), S6K1, ribosomal protein S6, and eukaryotic initiation factor 4E-binding protein 4E-BP1
Fukuda et al., Cancer Res 2003 (Colonic Neoplasms) : In contrast, phosphorylation of AKT is dependent on ERK and C-SRC activity
Vlotides et al., Endocrinology 2009 : Src inhibition with 4-amino-5- ( 4-chlorophenyl ) -7- ( t-butyl ) pyrazolo [ 3,4-d ] pyrimidine suppressed FGF-2 induced Akt and focal adhesion kinase, indicating effects downstream of FGF-2 induced Src activation
Morel et al., J Biol Chem 2002 (Arthritis, Rheumatoid...) : AS c-Src ODN inhibited Akt phosphorylation, confirming Src is upstream of PI3-kinase in IL-18 induced RA synovial fibroblast signaling
Murillo et al., Oncogene 2005 : The activation of c-Src by TGF-beta1 is EGFR dependent and is required for full Akt phosphorylation and cell survival
Schmitt et al., J Biol Chem 2002 (MAP Kinase Signaling System) : Interestingly, beta-adrenergic stimulation of both Rap1 and ERKs, but not Ras and AKT , can be blocked by a Src mutant ( SrcS17A ) that is incapable of being phosphorylated and activated by PKA ... Furthermore, a Src mutant ( SrcS17D ), which mimics PKA phosphorylation at serine 17, stimulates Rap1 activation, Rap1/B-Raf association, and ERK activation but does not stimulate Ras or AKT
Gingerich et al., Neuropharmacology 2008 : Finally, we demonstrate that Src kinase acts upstream of the PI3K/Akt pathway based on our finding that the selective Src inhibitor, PP2 ( 10microM ), blocked the increases in nNOS phosphorylation levels, NO production, and PI3K/Akt activity induced by ERbeta activation
Kim et al., Growth Factors 2007 : The ERK activatin was inhibited by the Src inhibitor and the Akt activation was inhibited by inhibitors of EGFR and Src
Lin et al., Toxicol Appl Pharmacol 2008 : LPS stimulated Src , PYK2, EGFR, and Akt phosphorylation and VCAM-1 expression were attenuated by the inhibitors of Src ( PP1 ), EGFR ( AG1478 ), PI3-K ( LY294002 and wortmannin ), and Akt ( SH-5 ), respectively, or transfection with siRNAs of Src or Akt and shRNA of p110
Zhang et al., Cancer Cell 2009 (Bone Neoplasms...) : Src mediates AKT regulation and cancer cell survival responses to CXCL12 and TNF related apoptosis inducing ligand ( TRAIL ), factors that are distinctively expressed in the bone metastasis microenvironment
Trevino et al., Cancer Res 2005 (Adenocarcinoma...) : Inhibition of c-Src activity resulted in decreased phosphorylation of Akt , p38, and extracellular signal regulated kinase ( Erk ) -1/2
Jin et al., J Biol Chem 2008 (Cell Transformation, Neoplastic) : Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt
Song et al., Cell Signal 2010 : In this study, we report that Src , c-Cbl, and PI3K are involved in the phosphorylation of Akt during TRAIL treatment
Lodeiro et al., PloS one 2009 : c-Src regulates Akt signaling in response to ghrelin via beta-arrestin signaling independent and -dependent mechanisms ... In summary this work reveals that c-Src is crucially involved in the ghrelin mediated Akt activation
Wu et al., Cell Physiol Biochem 2010 : Pressure activates Src dependent FAK-Akt and ERK1/2 signaling pathways in rat hepatic stellate cells
Wang et al., J Cell Physiol 2011 : Engagement of G ( i/o ) -- and G ( q ) -coupled ET ( B ) receptors by ET-1 led to activation of c-Src dependent phosphoinositide 3-kinase (PI3K)/Akt and p42/p44 mitogen activated protein kinase ( MAPK ) and then activated transcription factor nuclear factor-?B ( NF-?B )
Sung et al., Neurochem Res 2007 (Anoxia...) : Inhibitors of growth factor receptor ( AG1478 ) and Src ( PP2 ) and the antioxidant N-acetylcysteine did not affect activation of ERK and Akt , while the Ras and Raf inhibitors inhibited activation of ERK, but not Akt
Lei et al., Am J Physiol Lung Cell Mol Physiol 2011 : In summary, in adult rat AECs T3-stimulated Src kinase activity can activate both PI3K/Akt and MAPK/ERK1/2, and activation of Akt is necessary for T3-induced Na-K-ATPase activity
Kashiwagi et al., Biochem Biophys Res Commun 2008 (Lung Neoplasms) : More specifically, T3E dependent inhibition of Src induced Akt activation contributed to suppression of cell survival under hypoxia, and the reduction of fibrinolytic factors such as plasminogen activator-1(PAI-1) via the decrease of hypoxia-inducible factor-2alpha by T3E led to inhibition of hypoxic invasion
Hauck et al., EMBO J 2002 (Lung Neoplasms) : However, FRNK did not affect v-Src stimulated Akt activation, cell growth in soft agar, or subcutaneous tumor formation in nude mice
Duong et al., Cancer Res 2006 (Breast Neoplasms) : Mammalian two-hybrid assays revealed that AKT enhanced both SRC1 and GRIP1 recruitment to the ER beta-AF2 domain, and reporter gene analyses revealed that AKT and GRIP1 cooperatively potentiated ER beta mediated transcription to a level much greater than either factor alone
Park et al., Cancer Res 2006 (Glioblastoma...) : In addition, inhibitors of epidermal growth factor receptor ( EGFR ; AG490 and AG1478 ), Src ( PP2 ), and p38 ( SB203580 ), EGFR neutralizing antibody, and transfection of DN-Src and DN-p38 significantly blocked IR-induced Akt phosphorylation and MMP-2 secretion
Jin et al., Cancer Res 2007 (Cell Transformation, Neoplastic) : Suppression of c-Src by RNA interference in NIH3T3-ETV6-NTRK3 cells resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt
Madeira et al., J Vasc Res 2009 (MAP Kinase Signaling System) : This effect involves the intracellular formation of ROS in endothelial cells leading to the Src kinase/phosphoinositide 3-kinase/Akt dependent phosphorylation of eNOS
Sun et al., Am J Physiol Heart Circ Physiol 2009 (Disease Models, Animal...) : Taken together, we hypothesize that TSP1 antagonizes VEGF-driven Akt survival signaling in part through the recruitment of Fyn to membrane domains containing CD36, but when TSP1 is absent, an opposing Src recruitment contributes to VEGF-driven Akt phosphorylation and capillary survival
Li et al., Invest Ophthalmol Vis Sci 2013 (MAP Kinase Signaling System) : Active PKCa phosphorylates Src to induce PI-3K to phosphorylate AKT that subsequently activates the ERK1/2 cascade to stimulate goblet cell proliferation
Feng et al., Biosci Biotechnol Biochem 2012 (Insulin Resistance) : Palmitate contributes to insulin resistance through downregulation of the Src mediated phosphorylation of Akt in C2C12 myotubes ... Additionally, it inhibited the insulin stimulated phosphorylation of Src at Tyr416, causing a reduction in the Src mediated phosphorylation of Akt ... The findings indicate that palmitate contributes to insulin resistance by inhibiting the Src mediated phosphorylation of Akt in C2C12 myotubes, and this provides insight into the molecular mechanisms of FFA induced insulin resistance
Song et al., Journal of neuroinflammation 2012 (Neuroblastoma) : We also found that Src/PI3K/Akt inhibitors prevented LLLT stimulated Akt ( Ser473 and Thr308 ) phosphorylation and blocked Rac1 activity and actin based microglial phagocytosis, indicating the activation of Src/PI3K/Akt/Rac1 signaling pathway
Liu et al., Exp Cell Res 2011 : Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors ... Mechanical stretch augments insulin induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor mediated ERK and Akt activation
Haynes et al., J Biol Chem 2003 : Moreover, transfection of kinase-dead c-Src inhibited 17beta-estradiol induced Akt phosphorylation, whereas constitutively active c-Src increased basal Akt phosphorylation
Cheng et al., FEBS Lett 2004 (Neoplasms, Experimental) : Biochemical analysis revealed that the Cas SH3 domain selectively inhibited v-Src stimulated activations of AKT and JNK, but not ERK and STAT3
Fleming et al., Endocrinology 2006 : Interestingly, inhibition of Src activation blocked the ability of EGF, but not IGF-I, to activate AKT
Abid et al., J Biol Chem 2007 : The permissive role of NADPH oxidase on phosphoinositide 3-kinase-Akt-forkhead signaling is mediated at post-VEGF receptor levels and involves the nonreceptor tyrosine kinase Src
Yang et al., J Biol Chem 2013 (Diabetes Mellitus...) : The leucine facilitated insulin induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src ( PP2 ), PI3K ( LY294002 ), Gai protein ( pertussis toxin or siRNA against Gai1 gene, or ß-arrestin 2 ( siRNA ) )
Feng et al., Oncogene 2012 (Disease Progression...) : Inhibition of Src by Src inhibitors attenuated PDGF-A stimulated phosphorylation of Akt and Dyn2 and glioma cell migration
Hsu et al., Mol Nutr Food Res 2011 (Adenocarcinoma...) : Inhibition of the FAK/Src complex by glabridin also blocked AKT and ERK1/2 activation, resulting in reduced activation of RhoA as well as myosin light chain phosphorylation
Choudhury et al., Cell Signal 2006 : Expression of constitutively active c-Src increased Akt activity to the same extent as with PDGF ... Constitutively active c-Src augmented PDGF induced Akt activity, thus contributing to Akt signaling
Endo et al., Exp Hematol 2001 : These data indicate that SCF protects purified human GPA+c-kit+ cells from apoptosis and suggest that kit mediated Src kinase activation is involved in Akt activation and cell survival
Koga et al., Proc Natl Acad Sci U S A 2006 : Hsp90 inhibition transiently activates Src kinase and promotes Src dependent Akt and Erk activation
Cho et al., Mol Biol Cell 2013 (Atherosclerosis) : Apo(a) caused the disruption of VE-cadherin/ß-catenin complexes in a Src dependent manner, decreased ß-catenin phosphorylation, and increased phosphorylation of Akt and glycogen synthase kinase-3ß, ultimately resulting in increased nuclear translocation of ß-catenin ; all of these effects are downstream of apo(a) attenuation of phosphatase and tensin homologue deleted on chromosome 10 activity
Chabot et al., Mol Cell Biol 2009 : The increased phosphorylation of Src on Y529 under these conditions results in impaired Src and Akt activation ... Overall, our results reveal that despite its negative role on global VEGFR2 phosphorylation, DEP-1 is a positive regulator of VEGF mediated Src and Akt activation and endothelial cell survival
Tian et al., J Biol Chem 2009 : Mechanistically, both Src and caveolin-1 are required for ouabain induced activation of Akt and up-regulation of Na/K-ATPase
Steinle et al., Exp Eye Res 2005 (Choroidal Neovascularization) : BRL37344 treatment also increased choroidal endothelial cell invasion by 103 % above control values ; the invasion response was inhibited by PP2 ( Src inhibitor ), LY294002 ( PI3K inhibitor ), Akt inhibitor ( Akt-I ) , and matrix metalloproteinase 2/9 inhibitor ( MMP-I )
Jiang et al., J Biol Chem 2003 : Interaction between Src and a C-terminal proline-rich motif of Akt is required for Akt activation ... We also showed that phosphorylation of Tyr-315 in Akt induced by Src or EGF is dependent on the integrity of this proline-rich motif
Kim et al., Blood 2006 : Selective G ( 12/13 ) activation resulted in Src kinase activation, and Akt phosphorylation induced by costimulation of G ( 12/13 ) and Gi/Gz was inhibited by a Src kinase inhibitor but not by a Rho kinase inhibitor
Wu et al., Am J Physiol Lung Cell Mol Physiol 2005 : Inhibition of p38, Src , and EGFR kinases with pharmacological inhibitors markedly reduces Akt phosphorylation induced by Zn2+
Castoria et al., EMBO J 2001 (Breast Neoplasms) : The Src inhibitor, PP1, prevents hormone stimulation of Akt and PI3-kinase activities in MCF-7 cells
Morisco et al., Cardiovasc Res 2008 (Cardiomegaly) : beta-Adrenergic activation of Akt is mediated by Src , which associates with the endocytosis machinery and is necessary and sufficient to mediate beta-adrenergic hypertrophy
Rattmann et al., J Vasc Res 2012 : Natural product extract of Dicksonia sellowiana induces endothelium dependent relaxations by a redox-sensitive Src- and Akt dependent activation of eNOS in porcine coronary arteries
Lu et al., J Biol Chem 2003 (Breast Neoplasms) : Activated Src reduces the ability of PTEN to dephosphorylate phosphatidylinositols in micelles and promotes AKT translocation to cellular plasma membranes but does not alter PTEN activity toward water-soluble phosphatidylinositols
Díaz-Montero et al., Eur J Cancer 2006 (Osteosarcoma) : PI3-K/Akt mediated anoikis resistance of human osteosarcoma cells requires Src activation ... Furthermore, pharmacological inhibition of Src resulted in a decrease of Akt phosphorylation at Ser473
Gates et al., Am J Physiol Gastrointest Liver Physiol 2009 : Maximal cAMP-GEF mediated Akt phosphorylation as well as protection from bile acid induced apoptosis requires activation of Src-TYK and the EGFR
Tsai et al., Integr Cancer Ther 2011 (Carcinoma, Non-Small-Cell Lung...) : Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation
Kim et al., Mol Cancer Res 2008 (MAP Kinase Signaling System...) : Inhibition of c-Src attenuated Rac1 and p38 MAPK activations and Ser ( 473 ) phosphorylation of Akt
Fan et al., Anticancer Drugs 2010 : SF protection against TRAIL required c-Akt ; but unlike protection against adriamycin, it did not require Src signaling or the classical pathway of nuclear factor-kappaB activation
Duxbury et al., Cancer Res 2004 (Adenocarcinoma...) : Differential expression of CEACAM6 modulates Akt activity in a c-Src dependent manner, and CEACAM6 overexpression appears to protect cells from cytochrome c-induced caspase 3 activation and apoptosis
Buitrago et al., J Cell Biochem 2012 : Of relevance, Src and PI3K are involved in Akt activation and in MHC and myogenin increased expression by 1a,25 ( OH ) ( 2 ) D ( 3 )
Ichiki et al., Biochem Biophys Res Commun 2004 : GM6001, a matrix metalloproteinase inhibitor, and PP2, a Src family protein kinase inhibitor, suppressed 15-d-PGJ2- and TZDs induced phosphorylation of EGF-R and PDGFbeta-R as well as activation of ERK1/2 and Akt