GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:19033661
Citation |
Zhang, H, He, Y, Dai, S, Xu, Z, Luo, Y, Wan, T, Luo, D, Jones, D, Tang, S, Chen, H, Sessa, WC and Min, W (2008) AIP1 functions as an endogenous inhibitor of VEGFR2-mediated signaling and inflammatory angiogenesis in mice. J. Clin. Invest. 118:3904-16 |
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Abstract |
ASK1-interacting protein-1 (AIP1), a recently identified member of the Ras GTPase-activating protein family, is highly expressed in vascular ECs and regulates EC apoptosis in vitro. However, its function in vivo has not been established. To study this, we generated AIP1-deficient mice (KO mice). Although these mice showed no obvious defects in vascular development, they exhibited dramatically enhanced angiogenesis in 2 models of inflammatory angiogenesis. In one of these models, the enhanced angiogenesis observed in the KO mice was associated with increased VEGF-VEGFR2 signaling. Consistent with this, VEGF-induced ear, cornea, and retina neovascularization were greatly augmented in KO mice and the enhanced retinal angiogenesis was markedly diminished by overexpression of AIP1. In vitro, VEGF-induced EC migration was inhibited by AIP1 overexpression, whereas it was augmented by both AIP1 knockout and knockdown, with the enhanced EC migration caused by AIP1 knockdown being associated with increased VEGFR2 signaling. We present mechanistic data that suggest AIP1 is recruited to the VEGFR2-PI3K complex, binding to both VEGFR2 and PI3K p85, at a late phase of the VEGF response, and that this leads to inhibition of VEGFR2 signaling. Taken together, our data demonstrate that AIP1 functions as an endogenous inhibitor in VEGFR2-mediated adaptive angiogenesis in mice. |
Links |
PubMed PMC2575835 Online version:10.1172/JCI36168 |
Keywords |
Animals; Cattle; Cell Movement/genetics; Corneal Neovascularization/genetics; Corneal Neovascularization/metabolism; Disease Models, Animal; Endothelial Cells/metabolism; Humans; Inflammation/genetics; Inflammation/metabolism; Mice; Mice, Knockout; Neovascularization, Pathologic/genetics; Neovascularization, Pathologic/metabolism; Organ Specificity/genetics; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/metabolism; Signal Transduction/genetics; Vascular Endothelial Growth Factor A/genetics; Vascular Endothelial Growth Factor A/metabolism; Vascular Endothelial Growth Factor Receptor-2/genetics; Vascular Endothelial Growth Factor Receptor-2/metabolism; ras GTPase-Activating Proteins/genetics; ras GTPase-Activating Proteins/metabolism |
Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
involved_in |
GO:0031334: positive regulation of protein-containing complex assembly |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q5VWQ8 |
F |
Seeded From UniProt |
complete | ||
MOUSE:DAB2P |
involved_in |
GO:0030948: negative regulation of vascular endothelial growth factor receptor signaling pathway |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
MOUSE:DAB2P |
involved_in |
GO:0010596: negative regulation of endothelial cell migration |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
MOUSE:DAB2P |
involved_in |
GO:0035148: tube formation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
MOUSE:DAB2P |
involved_in |
GO:0001933: negative regulation of protein phosphorylation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
MOUSE:DAB2P |
involved_in |
GO:0016525: negative regulation of angiogenesis |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
MOUSE:DAB2P |
involved_in |
GO:0036324: vascular endothelial growth factor receptor-2 signaling pathway |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
MOUSE:DAB2P |
involved_in |
GO:0035924: cellular response to vascular endothelial growth factor stimulus |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
MOUSE:DAB2P |
involved_in |
GO:1900747: negative regulation of vascular endothelial growth factor signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:DAB2P |
involved_in |
GO:0030948: negative regulation of vascular endothelial growth factor receptor signaling pathway |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:DAB2P |
involved_in |
GO:0010596: negative regulation of endothelial cell migration |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:DAB2P |
involved_in |
GO:0035148: tube formation |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:DAB2P |
enables |
GO:0017124: SH3 domain binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
HUMAN:DAB2P |
enables |
GO:0043184: vascular endothelial growth factor receptor 2 binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P35968 |
F |
Seeded From UniProt |
complete | |
HUMAN:DAB2P |
enables |
GO:0043548: phosphatidylinositol 3-kinase binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
HUMAN:DAB2P |
involved_in |
GO:0016525: negative regulation of angiogenesis |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
HUMAN:DAB2P |
involved_in |
GO:0035924: cellular response to vascular endothelial growth factor stimulus |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
involved_in |
GO:0001934: positive regulation of protein phosphorylation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0010595: positive regulation of endothelial cell migration |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0031334: positive regulation of protein complex assembly |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0035148: tube formation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0045766: positive regulation of angiogenesis |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0046777: protein autophosphorylation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0035924: cellular response to vascular endothelial growth factor stimulus |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
involved_in |
GO:0001934: positive regulation of protein phosphorylation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
Notes
See also
References
See Help:References for how to manage references in GONUTS.
n
- GO:0030948 ! negative regulation of vascular endothelial growth factor receptor signaling pathway
- GO:0010596 ! negative regulation of endothelial cell migration
- GO:0001933 ! negative regulation of protein phosphorylation
- GO:0016525 ! negative regulation of angiogenesis
- GO:1900747 ! negative regulation of vascular endothelial growth factor signaling pathway
p
- GO:0043548 ! phosphatidylinositol 3-kinase binding
- GO:0045766 ! positive regulation of angiogenesis
- GO:0010595 ! positive regulation of endothelial cell migration
- GO:0001934 ! positive regulation of protein phosphorylation
- GO:0031334 ! positive regulation of protein-containing complex assembly
- GO:0046777 ! protein autophosphorylation
- GO:0005515 ! protein binding