Gene interactions and pathways from curated databases and text-mining

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Text-mined interactions from Literome

Huang et al., J Biol Chem 2002 : Inhibition of endogenous PTEN in cultured endothelial cells by adenovirus mediated overexpression of a dominant negative PTEN mutant ( PTEN-C/S ) enhanced VEGF mediated Akt phosphorylation, and this effect correlated with decreases in caspase-3 cleavage, caspase-3 activity, and DNA degradation after induction of apoptosis with tumor necrosis factor-alpha
Skaletz-Rorowski et al., Cardiovasc Res 2003 (Translocation, Genetic) : Furthermore, the ability of statins to promote Akt activation and translocation to the membrane is inhibited by cholesterol delivery to cells, but cholesterol loading had no effect on VEGF induced Akt activation
Wang et al., Biochem Biophys Res Commun 2008 : Moreover, Ly 294002, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K)/Akt significantly attenuated the VEGF synthesis stimulated by TGF-beta1
Basini et al., Biofactors 2007 : SA appear to be an antiangiogenic natural product by directly suppressing the proliferative effect of VEGF on endothelial cell line : this effect could be mediated by blocking the VEGF induced Akt activation
Lu et al., Microvasc Res 2009 (Lung Neoplasms...) : Furthermore, lenalidomide inhibited VEGF induced PI3K-Akt pathway signaling, which is known to regulate adherens junction formation
Basu et al., J Immunol 2010 : Furthermore, by Western blot analysis, we find that VEGF increases the phosphorylation and activation of ERK and Akt within CD4+CD45RO+ T cells
Masuda et al., J Exp Ther Oncol 2002 (Breast Neoplasms...) : These results suggest that EGCG inhibits VEGF production by inhibiting both the constitutive activation of Stat3 and NF-kappa B, but not extracellular-signal regulated kinase ( ERK ) or Akt , in these cells
Tsugawa et al., Frontiers in bioscience : a journal and virtual library 2002 (Disease Progression...) : PTEN can : 1 ) inhibit entry into the cell cycle by inhibiting G1 to S phase progression and arrest cell proliferation required for tissue reconstruction during injury healing ; 2 ) increase apoptosis by blocking Akt activation leading to increased Bad and Caspase-9 activities ; 3 ) inhibit hypoxia induced angiogenesis required for injury healing by blocking Akt mediated VEGF gene transcription ; 4 ) inhibit Akt mediated cell migration, i.e. re-epithelialization, which is also required for injury healing
Hur et al., Stem Cells 2007 (Ischemia) : As an underlying mechanism to control adhesion of EPCs to ECs, we found that Akt was activated in ECs of ischemic muscle by ischemia induced VEGF and SDF-1
Lugus et al., J Mol Cell Cardiol 2011 : In contrast, ablation of MFN1 led to the selective reduction of VEGF stimulated Akt-eNOS signaling
Pang et al., Cancer Res 2010 (Neovascularization, Pathologic...) : Celastrol suppressed the VEGF induced activation of AKT , mammalian target of rapamycin (mTOR), and ribosomal protein S6 kinase ( P70S6K )
Okuyama et al., J Biol Chem 2006 : MSC in which HIF-1 activity was inhibited by a dominant negative or RNA interference approach expressed markedly reduced levels of VEGFR1 and failed to migrate or activate AKT in response to VEGF or PLGF
Liu et al., Toxicological sciences : an official journal of the Society of Toxicology 2012 : Disruption of the JNK signaling pathway by treatment with the JNK inhibitor SP600125, siRNA knockdown of JNK, or genetic deficiency of the JNK1 or JNK2 gene abrogated As ( 3+ ) -induced S727 phosphorylation of Stat3, Akt activation , and the consequent release of vascular endothelial growth factor ( VEGF ) and migration of the cells
Klos et al., Cancer 2003 (Breast Neoplasms...) : Furthermore, Akt phosphorylation contributed to VEGF up-regulation and Akt phosphorylation was reduced more effectively by combined trastuzumab plus paclitaxel treatment compared with the other treatments
Tang et al., Mol Cancer Res 2006 (Breast Neoplasms...) : To explore the underlying signaling pathways used by EMMPRIN, we studied the involvement of phosphoinositide 3-kinase (PI3K)-Akt , mitogen activated protein kinase ( MAPK ), JUN, and p38 kinases in EMMPRIN mediated VEGF regulation
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 ... Furthermore, TNF- but not VEGF induced activation of VEGFR2, Akt , and EC migration are blunted in EC genetically deficient with Etk ... Taken together, our data demonstrated that TNF induces transactivation between Etk and VEGFR2, and Etk directly activates PI3K-Akt angiogenic signaling independent of VEGF induced VEGFR2-PI3K-Akt signaling pathway
Basini et al., Ann N Y Acad Sci 2007 : Sanguinarine inhibits VEGF induced Akt phosphorylation
Haeussler et al., J Biol Chem 2013 : Knockdown of H-Ras blocked VEGF induced PI3K dependent Akt ( Ser-473 ) and eNOS ( Ser-1177 ) phosphorylation and nitric oxide dependent cell migration, demonstrating the essential role of H-Ras
Gonzalez et al., J Biol Chem 2004 : We used siRNA to down-regulate Rac expression in BAEC, and we observed that Rac knockdown significantly reduced basal, S1P-, and VEGF induced Akt phosphorylation, suggesting a role for Rac activation in the caveolin siRNA mediated increase in Akt phosphorylation
Pratheeshkumar et al., PloS one 2012 (Neoplasm Invasiveness...) : Western blot analysis showed that luteolin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT , ERK, mTOR, P70S6K, MMP-2, and MMP-9 in HUVECs
Zhao et al., PloS one 2010 : In this study, we have shown that lovastatin inhibits ligand induced VEGFR-2 activation through inhibition of receptor internalization and also inhibits VEGF activation of AKT in human umbilical vein endothelial cells ( HUVEC ) and H28 MM cells employing immunofluorescence and Western blotting
Piccolo et al., J Mol Med (Berl) 2013 (Breast Neoplasms...) : Production of VEGF , that was restored by exposure of silenced cells to recombinant LGALS3BP, required an intact PI3k/Akt signaling
Penna et al., J Cell Mol Med 2013 : In the early phase of treatments, VEGF-A increased phospho-Akt , phospho-ERK-1/2 and phospho-PKCe compared to the untreated cells or FN-PAM-VEGF
Pyriochou et al., Int J Mol Med 2008 : In addition, PJ-34 abolished the migratory response to the prototype angiogenic factor vascular endothelial growth factor ( VEGF ) and reduced VEGF stimulated activation of members of the mitogen activated protein kinase family ( ERK1/2, p38 ), as well as Akt
Kou et al., Microcirculation 2008 (MAP Kinase Signaling System) : In contrast, application of the XO inhibitor oxypurinol or allopurinol inhibited VEGF stimulated Akt phosphorylation, indicating that endogenous XO promotes VEGF induced endothelial cell ( EC ) survival signaling
Clarke et al., PloS one 2012 (MAP Kinase Signaling System) : While DV was capable of phosphorylating AKT we show that AKT phosphorylation does not play a role in DV 's induction of VEGF expression or secretion using two separate inhibitors, LY294002 and Akt IV
Pan et al., Arterioscler Thromb Vasc Biol 2009 : Finally, G6PD tyrosine mutants ( Y428F, Y507F, and Y428F/Y507F ) decreased VEGF mediated Akt phosphorylation and EC migration
Sun et al., Am J Physiol Heart Circ Physiol 2009 (Disease Models, Animal...) : Thrombospondin-1 modulates VEGF-A mediated Akt signaling and capillary survival in the developing retina
He et al., Rheumatol Int 2011 (Arthritis, Rheumatoid) : TNFa- or hypoxia induced secretion of VEGF and IL-8 and expression of HIF-1a were hampered by treatment with the PI3 kinase inhibitor LY294002, suggesting that inhibition of PI3 kinase/Akt activation might inhibit VEGF and IL-8 secretion and HIF-1a expression induced by TNFa or hypoxia
Naruse et al., Diabetes 2006 (Atherosclerosis...) : Thus, activation of PKCbeta in endothelial cells and vascular tissue inhibits Akt activation by insulin and VEGF , inhibits Akt dependent eNOS regulation by insulin, and causes endothelial dysfunction in obesity associated insulin resistance
Feliers et al., Kidney Int 2005 (MAP Kinase Signaling System) : VEGF stimulated Akt phosphorylation in a PI3K dependent manner
Elayappan et al., Angiogenesis 2009 : Of interest, PEDF effectively abrogated VEGF mediated phosphorylation of PI3K/Akt
Suzuma et al., J Biol Chem 2002 : Stretch induced retinal vascular endothelial growth factor expression is mediated by phosphatidylinositol 3-kinase and protein kinase C (PKC)-zeta but not by stretch induced ERK1/2, Akt , Ras, or classical/novel PKC pathways ... Although stretch induced PI 3-kinase activation increased both Akt phosphorylation and activity of PKC-zeta, VEGF expression was dependent on PKC-zeta but not Akt
Chetty et al., Int J Cancer 2010 (Lung Neoplasms) : We also show that MMP-2 suppression disrupted PI3K dependent VEGF expression ; ectopic expression of myr-AKT restored VEGF inhibition
Smith , Acta Paediatr Suppl 2002 (Disease Models, Animal...) : In vitro, low IGF-1 prevents vascular endothelial growth factor induced activation of Akt , a kinase critical for vascular endothelial cell survival
Boulday et al., J Immunol 2006 : Moreover, we show that VEGF and IFN-gamma regulate the activation of the IP-10 promoter, and that the kinases PI3K, phosphoinositide dependent kinase 1, and Akt act as intermediary signaling molecules for cytokine-inducible IP-10 transcriptional activation in endothelial cells
Tanimoto et al., J Biol Chem 2002 : VEGF also activates eNOS through Flk-1/KDR, phosphoinositide 3-kinase, and Akt , which suggested that S1P and VEGF may share upstream signaling mediators ... S1P mediated phosphorylation of Flk-1/KDR, Akt , and eNOS were all inhibited by VEGF receptor tyrosine kinase inhibitors and by antisense Flk-1/KDR oligonucleotides
Murtagh et al., Cancer Res 2006 : Taxotere prevented the VEGF induced phosphorylation of focal adhesion kinase, Akt , and endothelial nitric oxide synthase (eNOS), all of which are Hsp90 client proteins
Li et al., Brain Res Mol Brain Res 2003 (Amyotrophic Lateral Sclerosis...) : Furthermore, VEGF induced downstream Akt activation promoted motor neuron-like NSC34 cell survival in the presence of mutant G93A-SOD1
Chabot et al., Mol Cell Biol 2009 : Reduced Src activity correlates with decreased phosphorylation of Gab1, an adapter protein involved in VEGF dependent Akt activation
Goetze et al., Biochem Biophys Res Commun 2002 : VEGF induced Akt phosphorylation was significantly inhibited by both PPARalpha- and gamma-activators
Jiang et al., Blood 2012 (Neovascularization, Pathologic) : In addition, we show that CD146 is required in VEGF induced VEGFR-2 phosphorylation, AKT/p38 MAPKs/NF-?B activation , and thus promotion of endothelial cell migration and microvascular formation
Tavora et al., EMBO Mol Med 2010 (Neoplasms...) : In addition, in vitro deletion of FAK in ECs resulted in reduced VEGF stimulated Akt phosphorylation and correlating reduced cellular proliferation as well as increased cell death
Ling et al., Biochem Biophys Res Commun 2007 (Carcinoma, Lewis Lung) : Endostar suppressed the VEGF induced tyrosine phosphorylation of KDR/Flk-1 ( VEGFR-2 ) as well as the overall VEGFR-2 expression and the activation of ERK, p38 MAPK, and AKT in HUVECs
Jiang et al., Curr Cancer Drug Targets 2008 (Neovascularization, Pathologic) : Recent studies have shown that AKT activation is necessary and sufficient to regulate VEGF and HIF-1 expression in human cancer cells ... It was found that AKT activation induces VEGF and HIF-1 expression through its two downstream molecules HDM2 and p70S6K1
Li et al., Exp Cell Res 2012 : Taken together, VEGFR-2 is expressed on primary human hair follicle DP cells and VEGF induces proliferation of DP cells through VEGFR-2/ERK pathway, but not p38, JNK or AKT signaling
Dimmeler et al., J Clin Invest 2001 (Coronary Disease) : Similarly, the potent angiogenic growth factor VEGF requires Akt to augment EPC numbers, suggesting an essential role for Akt in regulating hematopoietic progenitor cell differentiation
García-Maceira et al., Oncogene 2009 (Carcinoma, Hepatocellular) : Moreover, silibinin reduced hypoxia induced vascular endothelial growth factor ( VEGF ) release by HeLa and Hep3B cells, and this effect was potentiated by the PI3K/Akt inhibitor LY294002
Miao et al., Am J Physiol Cell Physiol 2003 : Consequently, wild-type kallistatin, but not kallistatin mutant K312A/K313A, suppressed VEGF induced phosphorylation of Akt
Ptaszynska et al., Mol Cancer Res 2010 (Neovascularization, Pathologic) : VEGF also increases LPA1 signaling, which in turn increases Akt2 expression
Li et al., J Huazhong Univ Sci Technolog Med Sci 2011 : VEGF stimulated Rap1 activity, phosphorylation of ERK and Akt , cyclin D1 expression and cell proliferation were repressed in HUVECs overexpressing Rap1GAP as compared to empty vector transfected control
Silvestre et al., Nat Med 2005 (Ischemia) : Using neutralizing antibodies and lactadherin-deficient animals, we show that lactadherin interacts with alphavbeta3 and alphavbeta5 integrins and alters both VEGF dependent Akt phosphorylation and neovascularization
van der Meer et al., International journal of cell biology 2009 : Moreover, activation of Akt and ERK1/2 in response to vascular endothelial growth factor was significantly lower in cells with low levels of caveolin-1
Fan et al., Mol Cancer Ther 2008 (Colorectal Neoplasms) : Inhibition of Akt or Src activation with wortmannin or PP2 blocked induction of VEGF-A by oxaliplatin in HT29 or RKO cells, respectively
Pore et al., Mol Biol Cell 2004 (Anoxia...) : Sp1 is involved in Akt mediated induction of VEGF expression through an HIF-1 independent mechanism ... Using both adenoviral vectors and a cell line permanently expressing constitutively active myristoylated Akt ( myrAkt ), we show that activation of Akt , which is downstream of PI3K, increases VEGF expression in vitro and increases angiogenesis in a Matrigel plug assay ... Transient transfection experiments using reporter constructs containing the VEGF promoter showed that up-regulation of VEGF by Akt is mediated through Sp1 binding sites located in the proximal promoter
Heo et al., BMB Rep 2009 : Furthermore, a pharmacological inhibitory study revealed that G ( alpha i/o ) -mediated phospholipase C, Akt , Erk, and p38 MAPK signaling are involved in this S1P induced expression of VEGF
Mathews et al., Arterioscler Thromb Vasc Biol 2008 : Vascular endothelial growth factor ( VEGF ) regulates endothelial cell survival via Akt activation downstream of VEGF receptor 2 (VEGFR2) activation
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
Zhang et al., American journal of physiology. Renal physiology 2011 : The p110d isoform contributes a minor amount of VEGF stimulated Akt activation
Lee et al., FEBS Lett 2010 : We demonstrate that reduction in Ca ( 2+ ) by chelating compound BAPTA-AM or by IP ( 3 ) -endoplasmic reticulum blocker 2-APB selectively inhibited VEGF induced activation of c-Src-PI3K-Akt but not ERK1/2 in human coronary artery endothelial cells ( HCAEC ) ... We also show that the selective inhibitory effects of NADPH oxidase knockdown on VEGF mediated activation of c-Src-PI3K-Akt signaling and cell proliferation in HCAEC can be reversed by increase in intracellular Ca ( 2+ )
Miao et al., Arterioscler Thromb Vasc Biol 2008 : Furthermore, adenoviral transduction of bovine aortic ECs with D88N-Hsp90 suppressed VEGF induced phosphorylation of Akt , eNOS, and NO release and the inhibitory effect was blocked by okadaic acid
Sengupta et al., Arterioscler Thromb Vasc Biol 2003 (MAP Kinase Signaling System...) : PTK787 inhibited the VEGF induced activation of Akt and ERKs, without affecting the HGF/SF induced phosphorylation
Hata et al., Jpn J Ophthalmol 2008 (Corneal Neovascularization) : In vitro, the inhibitory effects of fasudil on the VEGF dependent VEGF receptor 2 ( VEFGR2 or KDR ), extracellular signal related kinase ( ERK ) 1/2, Akt and myosin light chain ( MLC ) phosphorylation, as well as on the migration and proliferation of bovine retinal microvascular endothelial cells ( BRECs ) were analyzed with Western blotting, [ 3H ] -thymidine uptake, and modified Boyden chamber assay ... VEGF dependent phosphorylation of ERK1/2 and Akt were also partially but significantly attenuated by treatment with fasudil without affecting VEGFR2 ( KDR ) phosphorylation
Weigand et al., Angiogenesis 2005 (Breast Neoplasms...) : In addition, VEGF-A leads to increased phosphorylation of ERK1/2 and Akt indicating that VEGF-A stimulation plays a crucial role in the regulation of cell growth, apoptosis, survival and differentiation
Osuka et al., Stroke 2004 (Brain Ischemia) : The vascular endothelial growth factor ( VEGF ) contributes to activation of eNOS by Ca2+/calmodulin and also stimulates the protein kinase Akt , which directly phosphorylates eNOS on Ser1177 and increases enzyme activity
Edwards et al., Cancer Res 2002 (Glioblastoma) : Radiation- and vascular endothelial growth factor induced phosphorylation of Akt was inhibited by PI3K antagonists
Ruan et al., EMBO J 2012 : Axl is essential for VEGF-A dependent activation of PI3K/Akt ... These results elucidate the mechanism by which VEGF-A activates PI3K/Akt , and identify previously unappreciated potential therapeutic targets of VEGF-A-driven processes
Shiota et al., Arterioscler Thromb Vasc Biol 2010 (Disease Models, Animal...) : KNK437 inhibited the phosphorylation of VEGF induced Akt and endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells ... Silencing the Hsc70 gene by short interfering RNA abolished VEGF induced Akt phosphorylation and VEGF stimulated human umbilical vein endothelial cell migration and tube formation
Govindarajan et al., J Clin Invest 2007 (Cell Transformation, Neoplastic...) : Overexpression of Akt led to upregulation of VEGF , increased production of superoxide ROS, and the switch to a more pronounced glycolytic metabolism
Marumo et al., Hypertension 2006 : Consistent with the downregulation of VEGFR-2, VEGF induced phosphorylation of Akt was abolished in the progenitor cells after aldosterone treatment
Lo et al., International journal of molecular sciences 2013 : In parallel, VEGF induced JNK, PI3K and Akt activation
Gliki et al., Cell Biol Int 2002 : Here we examined the role of PKC in mediating VEGF induced Akt activation ... The PKC inhibitors GF109203X and calphostin C inhibited VEGF induced Akt activation ... Rottlerin and Go6976, inhibitors with specificities for PKC delta and alpha, respectively, also strongly inhibited VEGF induced Akt activation ... VEGF induced Akt activation was prevented by down-regulation of PKC induced by prolonged pretreatment with the phorbol ester, PMA ... The finding that PKC mediates VEGF induced Akt activation identifies a novel signal transduction pathway through which Akt can be regulated by growth factors acting through receptor protein tyrosine kinases, and indicates that PKC mediated Akt activity may play an essential role in VEGF stimulated angiogenesis
Banumathi et al., Invest Ophthalmol Vis Sci 2011 (Calcium Signaling) : The effects of the Ca ( 2+ ) /calmodulin dependent protein kinase II ( CaMKII ) inhibitor KN93 were also evaluated on VEGF induced Akt signaling and angiogenic activity ... These agents also inhibited VEGF induced phosphorylation of Akt , cell migration, proliferation, tubulogenesis, and sprouting angiogenesis ... VEGF induced phosphorylation of the proangiogenic protein Akt is critically dependent on this increase in [ Ca ( 2+ ) ] ( i ) and the subsequent activation of CaMKII
Cho et al., Biochem Biophys Res Commun 2005 : Thus, atRA decreases eNOS-Ser ( 1179 ) phosphorylation through a mechanism that depends on VEGF-KDR/Flk-1 mediated Akt phosphorylation but is independent of RARE, leading to reduction in NO production
Liao et al., Endocrinology 2010 : Caveolin-1 down-regulation suppressed VEGF stimulated phosphorylation of Akt , JNK, eNOS, c-Src, and FAK ; however, basal activities of c-Src and FAK were elevated in parallel with increased stress fiber formation and focal adhesion ... Caveolin-1 overexpression also inhibited VEGF induced phosphorylation of Akt , JNK, c-Src, FAK, and eNOS
Basini et al., J Reprod Dev 2007 : For this purpose, we studied the effect of 300 nM SA on the production of vascular endothelial growth factor ( VEGF ) by swine granulosa cells from follicles > 5 mm and on the activation of Akt , the main effector of the VEGF signalling pathway ... SA inhibited both VEGF production and VEGF induced Akt activation in swine granulosa cells
Rask-Madsen et al., Arterioscler Thromb Vasc Biol 2008 : Downregulation of PKC-epsilon abrogated VEGF stimulated phosphorylation of Akt at Ser473 and eNOS at Ser1179 and decreased VEGF stimulated NO synthase activity in intact cells ... By regulating VEGFR2 expression and activation, PKC-epsilon expression is critical for activation of Akt and eNOS by VEGF and contributes to VEGF stimulated Erk activation, whereas PKC-alpha has opposite effects
Bhattacharya et al., J Neurooncol 2013 (Brain Neoplasms...) : T11TS therapy in rodent glioma model significantly downregulated expression of VEGF along with its receptor VEGFR-2 and inhibited the expression of pro-survival PI3K/Akt/eNOS proteins in glioma associated brain endothelial cells
Iimuro et al., Circ Res 2004 (Ischemia...) : In cocultures of endothelial cells and fibroblasts, AM enhanced VEGF induced capillary formation, whereas in cultures of endothelial cells AM enhanced VEGF induced Akt activation
Endo et al., J Recept Signal Transduct Res 2003 : Inhibition of VEGFR-2 blocked activation of extracellular regulated-kinase, p38, Akt , and endothelial nitric oxide synthetase ( eNOS ) by VEGF , but did not inhibit p38 activation by the VEGFR-1-specific ligand, placental growth factor ( PIGF )
Segrelles et al., Carcinogenesis 2004 (Neovascularization, Pathologic...) : The induction of VEGF protein by Akt is associated with increased phosphorylation and thus activation of p70S6K and eIF4E binding protein 1, leading to increased VEGF translation
Ali et al., J Pharmacol Sci 2005 : M475271 inhibited VEGF induced extracellular signal regulated kinase1/2 ( ERK1/2 ) and p38 but not Akt activation in a concentration dependent manner
Liu et al., PloS one 2011 (Neovascularization, Pathologic) : The AKT and ERK inhibitors, LY294002 and U0126, suppressed HIF-1a and VEGF expression and angiogenesis
Amano et al., Hypertension 2003 (Ischemia) : Basal and VEGF mediated Akt phosphorylation in aortas was similar between eNOS-Tg and wild-type mice ... Our study demonstrates that overexpression of eNOS protein causes a marked increase in neocapillary formation in response to tissue ischemia without affecting ischemia induced VEGF expression or VEGF mediated Akt phosphorylation
Olszewska-Pazdrak et al., Am J Physiol Cell Physiol 2009 (Anoxia...) : VEGF induced activation of Akt , ERK1/2, p38, p70S6 kinases, and S6 ribosomal protein was also attenuated in hypoxic cells
Xu et al., Arterioscler Thromb Vasc Biol 2006 : TFPI-2 protein, but not recombinant KD1, blocked VEGF induced activation of both Akt and ERK1/2 in ECs
Bauer et al., Proc Natl Acad Sci U S A 2005 : In addition, VEGF mediated phosphorylation of Akt and its substrate, endothelial nitric oxide synthase, were significantly reduced in VEGF treated Cav-1 transgenic mice, compared with WT littermates
He et al., Cancer Chemother Pharmacol 2013 (Carcinoma, Non-Small-Cell Lung...) : EGCG inhibited HPV-16 oncoprotein induced angiogenesis conferred by NSCLC through the inhibition of HIF-1a protein expression and HIF-1a dependent expression of VEGF , IL-8, and CD31 as well as activation of Akt , suggesting that HIF-1a may be a potential target of EGCG against HPV related NSCLC angiogenesis
Xu et al., PloS one 2012 (Liver Neoplasms) : Addition of recombinant human VEGF attenuated the inhibitory effects of PP on PI3K/AKT pathway and the cancer phenotypes
Brouet et al., J Biol Chem 2001 : eNOS bound hsp90 can then recruit VEGF activated ( phosphorylated ) Akt to the complex, which in turn can phosphorylate eNOS
Riesterer et al., Oncogene 2004 : In this report, we demonstrate that VEGF controls the protein stability of the serine-threonine kinase PKB/Akt via inhibition of PKB/Akt protein degradation ... VEGF deprivation or blockage of the VEGF signal transduction cascade with the VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 resulted in a specific decrease of the PKB/Akt protein level and subsequent cellular restimulation with VEGF rescued its stability ... Real-time quantitative RT-PCR analysis demonstrated that VEGF does not regulate PKB/Akt gene expression ... On the other hand, broad range inhibitors of caspases and the proteasome complex prevented VEGF dependent downregulation of the PKB/Akt protein level indicating that PKB/Akt protein stability is regulated by VEGF controlled proteolysis ... Inhibition of the VEGF receptor and PKB/Akt-downstream PIK related mTOR-kinase by rapamycin also neutralized the VEGF-protective effect in an PKB/Akt gene expression independent way but results in proteolysis dependent reduction of PKB/Akt protein stability
Chen et al., Science signaling 2012 (Breast Neoplasms...) : PLD1 deficiency suppressed the activation of Akt and mitogen activated protein kinase signaling pathways by vascular endothelial growth factor in vascular endothelial cells, resulting in decreased integrin dependent cell adhesion to, and migration on, extracellular matrices, as well as reduced tumor angiogenesis in a xenograft model
Chen et al., Mol Nutr Food Res 2012 : Moreover, lycopene attenuated VEGF receptor-2 (VEGFR2) mediated phosphorylation of extracellular signal regulated kinase ( ERK ), p38, and Akt as well as protein expression of PI3K
Lee et al., Clin Cancer Res 2006 (Neoplasm Invasiveness...) : In OVCAR-3 and PC-3 cells, the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin/p70S6K and p42/p44 mitogen activated protein kinase pathways were required for LPA induced HIF-1alpha and VEGF expressions, whereas only the phosphoinositide 3-kinase/mammalian target of rapamycin/p70S6K pathway was important in SK-Hep1 cells
Eun et al., Biochem Biophys Res Commun 2004 : Our biochemical assays indicated that sanguinarine strongly suppressed basal and VEGF induced Akt phosphorylation, while it did not produce any changes in VEGF induced activation of ERK1/2 and PLCgamma1 ... Therefore, we conclude that sanguinarine is a potent antiangiogenic natural product, and its mode of action could involve the blocking of VEGF induced Akt activation
Hasaneen et al., Am J Physiol Lung Cell Mol Physiol 2007 : Our results show : 1 ) a significant increase in human lung microvascular endothelial cell ( HMVEC-L ) proliferation, migration, and tube formation following incubation in conditioned media ( CM ) from HASM cells exposed to mechanical strain ; 2 ) mechanical strain of HASM cells induced VEGF expression and release ; 3 ) VEGF neutralizing antibodies inhibited the proliferation, migration, and tube formations of HMVEC-L induced by the strained airway smooth muscle CM ; 4 ) mechanical strain of HASM induced a significant increase in hypoxia-inducible factor-1alpha ( HIF-1alpha ) mRNA and protein, a transcription factor required for VEGF gene transcription ; and 5 ) mechanical strain of HASM induced HIF-1alpha/VEGF through dual phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and ERK pathways
Lu et al., Am J Respir Cell Mol Biol 2010 (Neovascularization, Pathologic...) : Activation of PI3K/Akt by bleomycin also led to transcriptional activation and protein expression of hypoxia-inducible factor-1alpha ( HIF-1alpha ) and vascular endothelial growth factor , which contributed to the fibroproliferative and collagen inducing effects of bleomycin
Kim et al., Phytother Res 2012 : Ginsenoside Rg3 inhibits endothelial progenitor cell differentiation through attenuation of VEGF dependent Akt/eNOS signaling ... Moreover, treatment of CD34 derived EPCs with ginsenoside Rg3 resulted in the attenuation of VEGF dependent Akt/eNOS signaling as well as the inhibition of migration and tube formation
Takahashi et al., Mol Cell Biol 2002 (Disease Models, Animal...) : Akt mediated control of VEGF expression occurred at the level of transcription, and the hypoxia-inducible factor 1 regulatory element was dispensable for this regulation
LeBlanc et al., Am J Physiol Heart Circ Physiol 2008 : VEGF induced phosphorylation of Akt , but not eNOS, was significantly reduced in arterioles from old rats compared with arterioles from young rats
Slomiany et al., J Pharmacol Exp Ther 2006 (Anoxia) : IGF-1 stimulated VEGF promoter activity was phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR ( mammalian target of rapamycin ) -dependent, whereas VEGF secretion was only partially reduced by inhibition of PI3K/Akt/mTOR and HIF-1 activities
Jiang et al., Adv Cancer Res 2009 (Neoplasms...) : PI3K signaling regulates tumor growth and angiogenesis by activating AKT and other targets, and by inducing HIF-1 and VEGF expression
Xue et al., Arch Biochem Biophys 2007 (Carcinoma, Hepatocellular) : It inhibited VEGF induced activation of AKT and ERK signaling and reduced hypoxia enhanced HepG2 cell survivability
Izbicka et al., Anticancer Res 2005 (Breast Neoplasms...) : R115777 +/- paclitaxel inhibited HDJ-2 farnesylation, up-regulated RhoB, transiently lowered ( P ) ERK/ERK and ( P ) Akt/Akt , reduced Raf-1 and MEK and inhibited secretion of VEGF and MMP-1
Tahir et al., Cancer Biol Ther 2009 (Prostatic Neoplasms) : Downregulation of cav-1 in prostate cancer cell line PC-3 or human umbilical vein endothelial cells ( HUVECs ) through cav-1 siRNA significantly reduced basal and VEGF stimulated phosphorylation of VEGFR2 ( Y951 ), PLCgamma1 ( Y783 ) and/or Akt ( S473 & T308 ) relative to those in control siRNA treated cells ... Interestingly, treatment of HUVECs with cav-1 scaffolding domain ( CSD ) caused significant reduction in the VEGF stimulated phosphorylation of VEGFR2, PLCgamma1 and Akt suggesting that CSD inhibits cav-1 mediated angiogenic signaling
García-Caballero et al., Biochem Pharmacol 2013 : Data here shown altogether indicate that toluquinol has antiangiogenic effects both in vitro and in vivo that are exerted partly by suppression of the VEGF and FGF induced Akt activation of endothelial cells
Wang et al., Cell Signal 2005 (MAP Kinase Signaling System...) : Differential activation of the MEK/ERK and PI3K/AKT pathways that result in differential secretion IL-6, IL-8, TIMP-2 and VEGF were seen contingent on the cell type examined ; VEGF and TIMP-2 expression in PC3 cells are dependent on AKT activation and ERK activation in LNCaP and LNCaP C4-2B cells leads to IL-6 or IL-8 secretion
Smith , Growth Horm IGF Res 2004 (Neovascularization, Pathologic...) : In vitro, low IGF-I levels prevent VEGF induced activation of Akt , a kinase critical for vascular endothelial cell survival
Zang et al., Cell Signal 2013 : VEGF-A stimulated extracellular-signal regulated kinase, Akt and Rac1 activities in the wild-type cells whereas no such responses were noted in the knockout cells
Geretti et al., Mol Cancer Res 2010 (Melanoma) : It antagonized VEGF induced VEGFR-2/NRP2 complex formation and inhibited VEGF induced activation of AKT , a mediator of cell survival, without affecting activation of VEGFR-2
Kilic et al., FASEB J 2006 (Brain Ischemia) : Following 90-min episodes of middle cerebral artery occlusion, VEGF increased phosphorylated ( but not total ) Akt and ERK-1/-2 and reduced phosphorylated mitogen activated protein kinase/p38 and c-Jun NH2-terminal kinase (JNK)-1/-2 levels, at the same time decreasing inducible NO synthase expression in ischemic neurons
Zhu et al., Am J Pathol 2002 (MAP Kinase Signaling System) : VEGF induced biphasic and prolonged ( 15 minutes and 4 to 24 hours ) phosphorylation of p44/42 MAPK and Akt , while the effect of Ang-1 was transient and monophasic ( 15 minutes )
Xie et al., Ophthalmic Res 2013 (Retinal Neovascularization) : Knockdown of ILK effectively suppressed VEGF induced p38 mitogen activated protein kinase ( MAPK ) and Akt phosphorylation, but had no effects on VEGFR-2, extracellular signal regulated protein kinase and Jun N terminus kinase phosphorylation
Kilari et al., J Biol Chem 2013 (Hemangioma) : Silencing of ECSCR disrupts VEGF induced KDR activation and AKT and ERK phosphorylation and impairs VEGF stimulated KDR degradation
List et al., Exp Hematol 2004 (Acute Disease...) : In serum deprived KG1 and HL60 cells, rhu-VEGF stimulated rapid and sustained phosphorylation of Akt/PKB that was inhibited by the phosphatidyl inositol 3-kinase (PI3-K) kinase inhibitor wortmannin ... rhu-VEGF induced clonogenic response and Akt phosphorylation was abolished by the VEGF-RTK inhibitor SU-5416 at concentrations greater than 10 microM, whereas MEK inhibition by PD98059 ( 1 and 10 microM ) was ineffective
Kim et al., J Immunol 2006 (Arthritis, Rheumatoid...) : VEGF165 rapidly triggered phospho-Akt and phospho-ERK activity and then induced Bcl-2 expression in the rheumatoid synoviocytes
Goto et al., Int J Oncol 2008 (Carcinoma, Hepatocellular...) : Addition of conditioned media ( CM ) from tum-1 expressing PLC/PRF/5 cells significantly inhibited the spontaneous and vascular endothelial growth factor ( VEGF ) -induced proliferation and migration of human umbilical vein endothelial cells ( HUVEC ) in vitro with diminishing the VEGF induced phosphorylation of both Akt and extracellular signal regulated kinase ( ERK ) that are known to mediate VEGF induced proliferation and migration of endothelial cells
Shin et al., Invest New Drugs 2013 (Colorectal Neoplasms) : Notably, bevacizumab inhibited VEGF induced phosphorylation of VEGFR-2, Akt , and extracellular signal regulated kinase ( ERK ) ... In vivo, treatment with bevacizumab inhibited growth of xenografted tumors and attenuated VEGF induced phosphorylation of Akt and ERK
Berger et al., Journal of negative results in biomedicine 2006 : VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt : comparison of nerve growth factor and vascular endothelial growth factor
Pyriochou et al., Br J Pharmacol 2007 : On the other hand, C-18 blocked activation of members of the mitogen activated protein kinase family and of the Ser/Thr kinase Akt induced by both VEGF and Ang-1
Fu et al., PloS one 2013 : BBR also downregulated HIF-1a and VEGF expression and inhibited Akt and ERK phosphorylation
Banerjee et al., Biochemistry 2008 (Breast Neoplasms) : Neutralization of VEGF action by its antibody or inhibition of VEGF induced PI3K/Akt kinase activation by wortmannin, a PI3K/Akt specific inhibitor, results in inhibition of VEGF induced hAOSMC migration
Franklin et al., J Clin Endocrinol Metab 2003 : VEGF induced phosphorylation of Akt , as evident by both specific immunoblots and confocal microscopy, was significantly and rapidly reduced in the presence of IGFBP-3, as well as wortmannin
Stahmann et al., J Biol Chem 2010 : We demonstrate that AMPK does not mediate eNOS phosphorylation at serine residue 1177 or 633, NO- dependent cGMP generation, or Akt phosphorylation in response to VEGF
Maeno et al., J Biol Chem 2012 (Metabolic Diseases) : Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1 mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K
Frost et al., Oncogene 2007 (Multiple Myeloma...) : AKT activity regulates the ability of mTOR inhibitors to prevent angiogenesis and VEGF expression in multiple myeloma cells ... Internal ribosome entry site ( IRES ) -mediated cap independent translation is a salvage pathway for protein expression when mTOR is inhibited, so we analyzed a possible regulatory role of AKT on VEGF IRES activity ... These results support a mechanism whereby AKT prevents VEGF IRES activity in myeloma cells during mTOR inhibition resulting in a more complete abrogation of VEGF translation, and ultimately, angiogenesis
Sun et al., PloS one 2013 : Our results show that baicalein induced Epo and VEGF expression in a HIF1a- and PI3K/Akt dependent manner in neurons
Kurmasheva et al., Mol Cancer Ther 2007 (Anoxia) : Differential regulation of vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors ... Exogenous VEGF stimulated both Akt and extracellular signal regulated kinase 1/2 phosphorylation in six of seven rhabdomyosarcoma cell lines but in only one of seven neuroblastoma cells, suggesting autocrine stimulation predominantly in rhabdomyosarcoma cell lines
Abdelsaid et al., J Pharmacol Exp Ther 2010 (Anoxia...) : Expression of vascular endothelial growth factor , caspase-3, and poly ( ADP ribose ) polymerase ( PARP ), activation of Akt and p38 mitogen activated protein kinase ( MAPK ), and tyrosine nitration of the phosphatidylinositol (PI) 3-kinase p85 subunit were analyzed by Western blot
Meng et al., Am J Physiol Cell Physiol 2007 (Liver Neoplasms, Experimental...) : Moreover, Akt was involved in NF-kappaB dependent VEGF expression and angiogenesis
Pratheeshkumar et al., PloS one 2012 (Neovascularization, Pathologic...) : Western blot analysis showed that quercetin suppressed VEGF induced phosphorylation of VEGF receptor 2 and their downstream protein kinases AKT , mTOR, and ribosomal protein S6 kinase in HUVECs
Yang et al., Invest Ophthalmol Vis Sci 2009 (Anoxia...) : Role of PI3K/Akt and MEK/ERK in mediating hypoxia induced expression of HIF-1alpha and VEGF in laser induced rat choroidal neovascularization ... A well established rat model of CNV and cultured human retinal pigment epithelium ( hRPE ) was used to investigate the role of PI3K/Akt and MEK/ERK pathways in regulating HIF-1alpha and VEGF expression in CNV in rat and hRPE under hypoxia by immunohistochemistry, Western blot analysis, real-time PCR, and ELISA
Benndorf et al., Circ Res 2003 : We therefore investigated the effect of Ang II on VEGF induced Akt and eNOS phosphorylation ... Ang II diminished the VEGF induced phosphorylation of Akt and eNOS in endothelial cells, whereas the autophosphorylation of VEGF receptors was unaffected
Imai et al., Br J Haematol 2006 (Acute Disease...) : Finally, it was shown that the Akt phosphorylation was augmented by VEGF ( 165 ) in Kasumi-1, which was abrogated by VEGFR2 kinase inhibitor
Ghosh et al., J Biol Chem 2012 (MAP Kinase Signaling System...) : Therefore, based on these observations, it is hypothesized that the activation of PI3K/AKT and p38 MAPK by VEGF results in ETS-1 gene expression, which activates MMP-9 and MMP-13, leading to the invasion and scattering of SKOV-3 cells
Chiu et al., Mol Cell Biochem 2013 (Neovascularization, Pathologic) : Furthermore, ß ( 2 ) -GPI suppressed VEGF induced phosphorylation of VEGF receptor 2 (VEGFR2), extracellular signal regulated kinase 1/2 ( ERK1/2 ), and Akt
Fujio et al., J Biol Chem 1999 : In suspension cultures, VEGF stimulation was unable to activate Akt, and Akt protein levels were repressed in cells undergoing anoikis
Kobayashi et al., Pathobiology 2006 (Adenocarcinoma...) : We investigated the role of phosphatidyl inositol-3 OH kinase (PI3K)-Akt signaling in the regulation of HIF-1alpha and VEGF expression in human gastric adenocarcinoma
Li et al., Zhongguo Dang Dai Er Ke Za Zhi 2011 (Neuroblastoma) : The synthesis and secretion of VEGF can be inhibited by blocking TrkB-BDNF signal pathway with K252a or blocking the TrkB-BDNF downstream signal pathway PI3K/Akt with LY294002
Hayashi et al., Arterioscler Thromb Vasc Biol 2009 : FHL-2 suppresses VEGF induced phosphatidylinositol 3-kinase/Akt activation via interaction with sphingosine kinase-1 ... Importantly, overexpression of FHL-2 in ECs inhibited VEGF induced SK1 activity, phosphatidylinositol 3-kinase activity, and phosphorylation of Akt and eNOS
Jang et al., BMC cancer 2010 (Breast Neoplasms...) : Inhibition of PI3K/Akt signaling by ANT2 shRNA caused down-regulation of membrane-type 1 matrix metalloproteinase ( MT1-MMP ) and vascular endothelial growth factor ( VEGF ) expression, decreased matrix metalloproteinase 2 (MMP2) and MMP9 activity, and suppressed migration and invasion of breast cancer cells
Bellou et al., Molecular cancer 2012 (MAP Kinase Signaling System...) : 6-ME did not alter VEGF induced phosphorylation of p38 MAPK or AKT , compatible with the lack of effect on VEGF induced migration and survival of endothelial cells
Xie et al., J Sex Med 2005 (Erectile Dysfunction...) : VEGF signaling leads to the phosphorylation of Akt and endothelial nitric oxide synthase ( p-Akt and p-eNOS )
Takai et al., Mol Cell Endocrinol 2007 : In the present study, we investigated the role of Akt/protein kinase B in the FGF-2 stimulated VEGF release in these cells ... Taken together, our findings strongly suggest that PI3-kinase/Akt plays an inhibitory role in FGF-2 induced VEGF release in osteoblasts
Sakai et al., J Dent Res 2010 : VEGF induced ERK and AKT phosphorylation ( indicative of differentiation ), while inhibiting phosphorylation of STAT3 ( indicative of ` stemness ' )
Takahashi et al., J Biol Chem 2003 : In bovine aortic endothelial cells ( BAECs ), the effects of vascular endothelial growth factor ( VEGF ) and insulin on eNOS-HSP90-Akt complex formation and eNOS activation were compared
Zhang et al., Exp Cell Res 2006 (Keloid) : Our results also indicated that the enhancement of hypoxia mediated activation of ERK1/2 and Akt requires direct cell-cell interaction between mast cells and keloid fibroblasts, and activation of both ERK1/2 and Akt is involved in the hypoxia dependent HIF-1alpha protein accumulation and VEGF expression in the co-culture system
Zingg et al., Cancer Res 2004 (Lung Neoplasms) : More importantly, radiation induced PKB/Akt phosphorylation in endothelial cells was strongly down-regulated by the VEGF receptor tyrosine kinase inhibitor, whereas the ErbB receptor tyrosine kinase inhibitor did not affect PKB/Akt stimulation in response to irradiation ... These data demonstrate that ionizing radiation induces VEGF ligand independent but VEGF receptor dependent PKB/Akt activation in endothelial cells and that PI3K/Akt pathway activation by radiation occurs in a differential cell type and receptor dependent pattern
Beierle et al., J Surg Res 2005 (Neuroblastoma) : We have found that exposure of human neuroblastoma cells to exogenous VEGF results in an increased expression of survivin protein and phosphorylated Akt , and inhibition of PI3-kinase abrogates those effects
Leung et al., Blood 2006 : Moreover, loss of gng2 function inhibits the ability of VEGF to promote the angiogenic sprouting of blood vessels by attenuating VEGF induced phosphorylation of phospholipase C-gamma1 ( PLCgamma1 ) and serine/threonine kinase ( AKT )
Dai et al., Oncogene 2009 : In turn, OPN induced VEGF activates PI3K/AKT and the ERK1/2 pathway as a positive feedback signal
Kanda et al., J Cell Mol Med 2007 : Downregulation of Fes neither affected VEGF-A induced autophosphorylation of VEGF receptor 2 nor mitogen activated protein kinase activation, but markedly decreased Akt activation
Gerber et al., J Biol Chem 1998 : Endothelial cells cultured in the presence of VEGF and the Flk-1/KDR-selective VEGF mutant induced phosphorylation of the serine-threonine kinase Akt in a PI3-kinase dependent manner ... Akt activation was not detected in response to stimulation with placenta growth factor or an Flt-1-selective VEGF mutant