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Accession number;06A0569733
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| Title;Signal Transduction via Vascular Endothelial Growth Factor (VEGF) Receptors and Their Roles in Atherogenesis |
| Author;
MATSUMOTO TARO
(Advanced Medical Res. Center, Nihon Univ. School of Medicine)
MUGISHIMA HIDEO
(Advanced Medical Res. Center, Nihon Univ. School of Medicine)
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Journal Title;J Atheroscler Thromb
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Journal Code:L2187A
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ISSN:1340-3478
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VOL.13;NO.3;PAGE.130-135 (J-STAGE)(2006)
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| Figure&Table&Reference;FIG.4, TBL.3, REF.42 |
| Pub. Country;Japan |
| Language;English |
| 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 C.GAMMA.1 (PLC-.GAMMA.1) and Shb. Activation of PLC-.GAMMA.1 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. (Author abst.) |
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