Signal Transduction via Vascular Endothelial Growth Factor (VEGF) Receptors and Their Roles in Atherogenesis
Open Access
- 1 January 2006
- journal article
- review article
- Published by Japan Atherosclerosis Society in Journal of Atherosclerosis and Thrombosis
- Vol. 13 (3), 130-135
- https://doi.org/10.5551/jat.13.130
Abstract
Vascular endothelial growth factor (VEGF)-A plays a critical role in vascular development and angiogenesis through its binding and activation of VEGF receptor-2 (VEGFR-2). The binding of VEGF-A to VEGFR-2 causes receptor dimerization, kinase activation and autophosphorylation of specific tyrosine residues within the dimeric complex. Tyrosine(Y)951 in the kinase-insert domain, Y1054 and Y1059 in the kinase domain and Y1175 and Y1214 in the C-terminal tail have been shown to serve as autophosphorylation sites. Phosphorylated Y1175 creates a binding site for phospholipase Cγ1 (PLC-γ1) and Shb. Activation of PLC-γ1 and Shb regulates VEGF-A-dependent cell proliferation and cell migration, respectively. Phosphorylated Y951 binds and mediates tyrosine phosphorylation of the T-cell-specific adaptor protein (TSAd), which is expressed in endothelial cells. Y951-mediated coupling of VEGFR-2 and TSAd is critical for VEGF-A-induced cell migration and actin reorganization, and for pathological angiogenesis. These phosphorylation sites may be useful targets for the development of anti-angiogenic therapies to treat atherosclerosis and cancer.Keywords
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