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HSP90AA1 — VEGFA
Pathways - manually collected, often from reviews:
-
NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2:
Hsp90 (HSP90AA1)
→
VEGFR2 (dimer)/VEGFA (dimer) complex (KDR-VEGFA)
(modification, collaborate)
Soldi et al., EMBO J 1999, Rousseau et al., J Biol Chem 2000, Borges et al., J Biol Chem 2000, Masson-Gadais et al., Cell Stress Chaperones 2003, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2:
Hsp90 (HSP90AA1)
→
VEGFR2 (dimer)/VEGFA (dimer)/Hsp90/alphav/beta3 Integrin/Vitronectin complex (KDR-VEGFA-HSP90AA1-VTN-ITGAV-ITGB3)
(modification, collaborate)
Soldi et al., EMBO J 1999, Rousseau et al., J Biol Chem 2000, Borges et al., J Biol Chem 2000, Masson-Gadais et al., Cell Stress Chaperones 2003, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2:
alphav/beta3 Integrin/Vitronectin complex (VTN-ITGAV-ITGB3)
→
VEGFR2 (dimer)/VEGFA (dimer)/Hsp90/alphav/beta3 Integrin/Vitronectin complex (KDR-VEGFA-HSP90AA1-VTN-ITGAV-ITGB3)
(modification, collaborate)
Soldi et al., EMBO J 1999, Rousseau et al., J Biol Chem 2000, Borges et al., J Biol Chem 2000, Masson-Gadais et al., Cell Stress Chaperones 2003, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2:
VEGFR2 (dimer)/VEGFA (dimer) complex (KDR-VEGFA)
→
VEGFR2 (dimer)/VEGFA (dimer)/Hsp90/alphav/beta3 Integrin/Vitronectin complex (KDR-VEGFA-HSP90AA1-VTN-ITGAV-ITGB3)
(modification, collaborate)
Soldi et al., EMBO J 1999, Rousseau et al., J Biol Chem 2000, Borges et al., J Biol Chem 2000, Masson-Gadais et al., Cell Stress Chaperones 2003, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Integrins in angiogenesis:
Hsp90 (HSP90AA1)
→
VEGF/Rho/ROCK/alphav/beta3 Integrin complex (KDR-VEGFA-HSP90AA1-RHOA-ROCK1-ITGAV-ITGB3)
(modification, collaborate)
Soldi et al., EMBO J 1999, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Integrins in angiogenesis:
Hsp90 (HSP90AA1)
→
VEGFR2 homodimer/VEGFA homodimer complex (KDR-VEGFA)
(modification, collaborate)
Soldi et al., EMBO J 1999, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Integrins in angiogenesis:
ROCK (ROCK1)
→
VEGF/Rho/ROCK/alphav/beta3 Integrin complex (KDR-VEGFA-HSP90AA1-RHOA-ROCK1-ITGAV-ITGB3)
(modification, collaborate)
Soldi et al., EMBO J 1999, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Integrins in angiogenesis:
alphav/beta3 Integrin complex (ITGAV-ITGB3)
→
VEGF/Rho/ROCK/alphav/beta3 Integrin complex (KDR-VEGFA-HSP90AA1-RHOA-ROCK1-ITGAV-ITGB3)
(modification, collaborate)
Soldi et al., EMBO J 1999, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Integrins in angiogenesis:
VEGF/Rho/ROCK/alphav/beta3 Integrin complex (KDR-VEGFA-HSP90AA1-RHOA-ROCK1-ITGAV-ITGB3)
→
VEGFR2 homodimer/VEGFA homodimer complex (KDR-VEGFA)
(modification, collaborate)
Soldi et al., EMBO J 1999, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Integrins in angiogenesis:
VEGF/Rho/ROCK/alphav/beta3 Integrin complex (KDR-VEGFA-HSP90AA1-RHOA-ROCK1-ITGAV-ITGB3)
→
RhoA (RHOA)
(modification, collaborate)
Soldi et al., EMBO J 1999, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
Evidence: assay, physical interaction
-
NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2:
None
→
VEGFR2 (dimer)/VEGFA (dimer)/Hsp90/alphav/beta3 Integrin/Vitronectin complex (KDR-VEGFA-HSP90AA1-VTN-ITGAV-ITGB3)
(modification, collaborate)
Le Boeuf et al., J Biol Chem 2004
Evidence: mutant phenotype
-
NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2:
RHOA/GDP complex (RHOA)
→
VEGFR2 (dimer)/VEGFA (dimer)/Hsp90/alphav/beta3 Integrin/Vitronectin complex (KDR-VEGFA-HSP90AA1-VTN-ITGAV-ITGB3)
(modification, collaborate)
Le Boeuf et al., J Biol Chem 2004
Evidence: mutant phenotype
-
NCI Pathway Database Integrins in angiogenesis:
VEGF/Rho/ROCK/alphav/beta3 Integrin complex (KDR-VEGFA-HSP90AA1-RHOA-ROCK1-ITGAV-ITGB3)
→
FAK (PTK2)
(modification, activates)
Le Boeuf et al., Mol Biol Cell 2006, Abedi et al., J Biol Chem 1997
Evidence: mutant phenotype, assay, physical interaction
-
Reactome Reaction:
HSP90AA1
→
VEGFA
(reaction)
Schaller et al., Biochem J 2001, Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
-
Reactome Reaction:
HSP90AA1
→
VEGFA
(indirect_complex)
Le Boeuf et al., J Biol Chem 2004, Le Boeuf et al., Mol Biol Cell 2006
-
WikiPathways Aryl Hydrocarbon Receptor:
Complex of AIP-AHR-AIP-HSP90AA1-HSP90AA1
→
VEGFA
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Dias et al., Blood 2002
(Leukemia...) :
VEGF increased the expression of
Hsp90 by interacting with KDR and activating the mitogen activated protein kinase cascade ... In turn, Hsp90 modulated Bcl-2 expression, as shown by a complete blockage of
VEGF induced Bcl-2 expression and binding to
Hsp90 by the Hsp90-specific inhibitor geldanamycin ( GA ) ... GA also blocked the
VEGF induced
Hsp90 binding to APAF-1 on leukemic cells, a mechanism shown to inhibit apoptosis
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
Masson-Gadais et al., Cell Stress Chaperones 2003
:
The chaperone
Hsp90 is found in a complex that coprecipitates with inactivated VEGFR2, and the association is
increased by
VEGF and decreased by geldanamycin, a specific inhibitor of Hsp90 mediated events
Duval et al., Mol Biol Cell 2007
:
Src mediated phosphorylation of
Hsp90 in
response to
vascular endothelial growth factor ( VEGF ) is required for VEGF receptor-2 signaling to endothelial NO synthase ...
VEGF signaling to eNOS is principally
mediated by an Akt dependent phosphorylation of eNOS and by increased association of eNOS to the molecular chaperone,
heat-shock protein 90 kDa (Hsp90) ... Tyrosine phosphorylation of
Hsp90beta in
response to
VEGF is dependent on internalization of the VEGFR-2 and on Src kinase activation
Lang et al., Clin Cancer Res 2007
(Neovascularization, Pathologic...) :
Effects of
Hsp90 inhibition ( 17-AAG ) on
vascular endothelial growth factor were determined by ELISA and real-time PCR
Lang et al., Hepatology 2009
(Carcinoma, Hepatocellular...) :
Furthermore,
Hsp90 inhibition reduced the expression of platelet derived growth factor-receptor-beta ( PDGF-Rbeta ) on VSMCs, and
diminished vascular endothelial growth factor-receptor 2 ( VEGFR-2 ) expression on ECs, which further improves the anti-angiogenic capacity of this regimen
Hackl et al., Surgery 2010
(Acute Disease...) :
Effects of
HSP90 inhibition on the activation of signaling intermediates, expression of
vascular endothelial growth factor ( VEGF ), and hepatocyte growth factor (HGF) were investigated in primary human hepatocytes ( PHHs ) in vitro ... Inhibition of HSP90 effectively diminished the constitutive phosphorylation of Akt, Erk, and STAT3 in PHHs. Conversely, inhibition of
HSP90 significantly
increased the expression of both
VEGF and HGF mRNA, and induced HSP70 protein in PHH cultures in vitro
Bohonowych et al., Journal of oncology 2010
:
The four main topics addressed include ( 1 )
Hsp90 mediated regulation of
HIF/VEGF signaling, ( 2 ) chaperone dependent regulation of HIF independent VEGF mediated angiogenesis, ( 3 ) Hsp90 dependent targeting of key proangiogenic receptor tyrosine kinases and modulation of drug resistance, and ( 4 ) consideration of factors such as tumor microenvironment that pose several challenges for the clinical efficacy of anti-angiogenic therapy and Hsp90 targeted strategies
Desjardins et al., Arterioscler Thromb Vasc Biol 2012
:
These results reveal that modulation of
Hsp90 activity by AHA1
regulates VEGF signaling to eNOS and angiogenesis