Vascular endothelial cell growth factor (VEGF) mediates the activation of vascular permeability (VP) and angiogenesis in vivo. Previous studies have revealed that the activation of the Src family kinases, downstream of vascular endothelial cell growth factor (VEGF) receptor 2, appears to be important in endothelial cell responses to VEGF. For example we have linked Src kinases to the activation of VEGF-mediated VP. In addition Src kinases serve to regulate the Ras-map kinase. These studies will focus on the molecular targets of Src that are critical for VEGF-mediated effects in ECs. In this proposal, I will test the hypothesis that Src-induced phosphorylation of adherent's junction proteins (catenin and cadherin) is a critical event for a vascular permeability response, and that Src-mediated phosphorylation of focal adhesion kinase and Raf-1 kinase arecritical regulators of Erkl and Erk2 activation and thereby influence VEGF-mediated angiogenesis pathway critical for VEGF-mediated angiogenesis.
