◀ Back to NOS3
KDR — NOS3
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
NOS3
→
KDR
(increases, NOS3 Activity)
Evidence: an important mechanism through which VEGF could induce prolonged NO production is increased expression of eNOS mRNA and protein the mechanism mediating VEGF-stimulated eNOS expression is unclear, but the effect appears to occur via activation of VEGFR2
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NCI Pathway Database SHP2 signaling:
VEGFR2 (dimer)/VEGFA (dimer) complex (KDR-VEGFA)
→
GAB1/SHP2/PKA/eNOS complex (GAB1-PTPN11-PRKACA-NOS3)
(modification, activates)
Lu et al., Proc Natl Acad Sci U S A 2011
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database SHP2 signaling:
VEGFR2 (dimer)/VEGFA (dimer) complex (KDR-VEGFA)
→
eNOS (NOS3)
(modification, activates)
Lu et al., Proc Natl Acad Sci U S A 2011
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2:
VEGFR2 (dimer)/VEGFA (dimer) complex (KDR-VEGFA)
→
GAB1/SHP2/PKA/eNOS complex (GAB1-PTPN11-PRKACA-NOS3)
(modification, activates)
Lu et al., Proc Natl Acad Sci U S A 2011
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2:
VEGFR2 (dimer)/VEGFA (dimer) complex (KDR-VEGFA)
→
eNOS (NOS3)
(modification, activates)
Lu et al., Proc Natl Acad Sci U S A 2011
Evidence: mutant phenotype, physical interaction
Text-mined interactions from Literome
Shen et al., J Biol Chem 1999
:
A
KDR receptor-selective mutant
increased eNOS expression, whereas an Flt-1 receptor-selective mutant did not
Tanimoto et al., J Biol Chem 2002
:
These data are the first to establish a critical
role of
Flk-1/KDR in S1P stimulated
eNOS phosphorylation and activation
Duval et al., J Biol Chem 2003
:
Moreover, expression of Cbl in contrast to 70Z/3-Cbl inhibits the
Flk-1 dependent activation of
eNOS and, thus, NO release
Miura et al., Hypertension 2003
:
Our results showed that, in HCECs, stimulation of the B2 receptor leads to the transactivation of
KDR/Flk-1 , as well as to
eNOS activation , which induces tube formation
Jin et al., Circ Res 2003
:
Flow stimulated
VEGFR2 recruits phosphoinositide 3-kinase and
mediates activation of Akt and
eNOS ... Decreasing
VEGFR2 expression with antisense VEGFR2 oligonucleotides significantly
attenuates activation of Akt and
eNOS
Escribano et al., Clin Sci (Lond) 2004
(Colonic Neoplasms) :
Overexpression of
eNOS , VEGF and its receptor Flk-1 occurred early after azoxymethane administration in rat colonic tissue, even before morphological changes associated with tumour generation were observed, and aspirin
prevented the overexpression of both eNOS and VEGF receptor
Flk-1
Jin et al., J Biol Chem 2005
:
Gab1 phosphorylation as well as activation of Akt and
eNOS by flow was
inhibited by the Src kinase inhibitor PP2 ( 4-amino-5- ( 4-chlorophenyl ) -7- ( t-butyl ) pyrazolo [ 3,4-d ] pyrimidine ) and
VEGFR2 kinase inhibitors SU1498 and VTI, suggesting that flow mediated Gab1 phosphorylation is Src kinase dependent and VEGFR2 dependent
Cai et al., Microvasc Res 2006
:
Suppression of eNOS expression only abolished endothelial cell proliferation at VEGF concentrations above 20 ng/ml. Taken together, these results indicate that activation of
VEGFR-2 by VEGF
enhances SH-PTP1 activity and
eNOS expression, which in turn lead to two diverse events : one is that SH-PTP1 dephosphorylates VEGFR-2 and ERK/MAPK, which weaken VEGF mitogenic activity, and the other is that eNOS increases nitric oxide production which in turn lowers SH-PTP1 activity via S-nitrosylation
Grummer et al., Biochem J 2009
:
The selective VEGFR-1 agonist PlGF ( placental growth factor ) -1 elicits only a modest activation of eNOS in P-UAECs compared with VEGF ( 165 ), whereas the
VEGFR-2 kinase inhibitor
blocks VEGF ( 165 ) -stimulated
eNOS activation, suggesting VEGF ( 165 ) predominantly activates eNOS via VEGFR-2 ... Although VEGF ( 165 ) also activates ERK ( extracellular-signal regulated kinase ) -1/2, this is not necessary for eNOS activation since U0126 blocks ERK-1/2 phosphorylation, but not eNOS activation, and the
VEGFR-2 kinase inhibitor
inhibits eNOS activation, but not ERK-1/2 phosphorylation