Selective requirement for Src kinases during VEGF-induced angiogenesis andvascular permeability

Src kinase activity was found to protect endothelial cells from apoptosis d uring vascular endothelial growth factor (VEGF)-, but not basic fibroblast growth factor (bFGF)-, mediated angiogenesis in chick embryos and mice. In fact, retroviral targeting of kinase-deleted Src to tumor-associated blood vessels suppressed angiogenesis and the growth of a VEGF-producing tumor. A lthough mice lacking individual Src family kinases (SFKs) showed normal ang iogenesis, mice deficient in pp60(c-src) or pp62(c-yes) showed no VEGF-indu ced vascular permeability (VP), yet fyn(-/-) mice displayed normal VP. In c ontrast, inflammation-mediated VP appeared normal in Src-deficient mice. Th erefore, VEGF-, but not bFGF-, mediated angiogenesis requires SFK activity in general, whereas the VP activity of VEGF specifically depends on the SFK s, Src, or Yes.