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AKT2 — VEGFA
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