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Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells

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dc.contributor.advisor Abu-Ghazaleh, Robin
dc.contributor.author Abu-Ghazaleh, Robin
dc.contributor.author Kabir, Jahangir
dc.contributor.author Jia, Haiyan
dc.contributor.author Lobo, Mel
dc.contributor.author Zachary, Ian
dc.date.accessioned 2019-10-08T11:03:49Z
dc.date.available 2019-10-08T11:03:49Z
dc.date.issued 2001
dc.identifier.citation Abu-Ghazaleh R, Kabir J, Jia H, Lobo M, Zachary I. Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells. Biochem J. 2001;360(Pt 1):255–264. doi:10.1042/0264-6021:3600255 en_US
dc.identifier.other 10.1042/0264-6021:3600255
dc.identifier.uri http://scholar.ppu.edu/handle/123456789/1753
dc.description.abstract Vascular endothelial growth factor (VEGF) stimulates the tyrosine phosphorylation of focal adhesion kinase (FAK), increases focal adhesion formation and is chemotactic for human umbilical-vein endothelial cells (HUVECs). In the present study we identified the major sites of VEGF-induced FAK tyrosine phosphorylation and investigated the mechanism mediating this pathway in the action of VEGF. VEGF increased the focal adhesion localization of FAK phosphorylated at Tyr-397 (Y397) and Y861 but stimulated a marked increase in phosphorylation at Y861 without significantly affecting the total level of phospho-Y397 FAK. Inhibition of Src with the specific inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) completely blocked VEGF-induced Y861 phosphorylation without decreasing the level of phospho-Y397 FAK. We also examined the role of Src in mediating endothelial functions of VEGF in which FAK has been implicated as having a role. PP2 markedly inhibited VEGF-induced chemotaxis and wound-healing cell migration. The Src inhibitor also decreased the anti-apoptotic effect of VEGF determined by surface staining of annexin V but did not increase FAK proteolysis or prevent the VEGF-dependent inhibition of FAK proteolysis. In contrast, the specific PtdIns 3-kinase inhibitor LY294002 induced apoptosis and markedly decreased p125(FAK) expression and increased FAK proteolysis but had little effect on Y861 phosphorylation. These findings identify Src-dependent FAK phosphorylation at Y861 as a novel VEGF-induced signalling pathway in endothelial cells and suggest that this pathway might be involved in the mechanisms mediating VEGF-induced endothelial cell migration and anti-apoptosis. en_US
dc.description.sponsorship This work was supported by British Heart Foundation, grants PG/97036 and BS/94001 (to I. Z.). en_US
dc.language.iso en en_US
dc.publisher Portland Press Ltd en_US
dc.subject chemotaxis en_US
dc.subject endothelium en_US
dc.subject KDR en_US
dc.subject survival en_US
dc.title Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells en_US
dc.type Article en_US


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