Selective Requirement for Src Kinases during VEGF-Induced Angiogenesis and Vascular Permeability

• Published in: Molecular cell Vol. 4; no. 6; pp. 915 - 924
• Main Authors: Eliceiri, Brian P, Paul, Robert, Schwartzberg, Pamela L, Hood, John D, Leng, Jie, Cheresh, David A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.1999
• Subjects: Animals; Apoptosis - drug effects; Apoptosis - physiology; Capillary Permeability - drug effects; Capillary Permeability - physiology; Chick Embryo; Endothelial Growth Factors - pharmacology; Endothelial Growth Factors - physiology; Endothelium, Vascular - pathology; Endothelium, Vascular - physiology; fibroblast growth factor (basic); Fibroblast Growth Factor 2 - pharmacology; Lymphokines - pharmacology; Lymphokines - physiology; Mice; Mice, Knockout; Neovascularization, Pathologic; Neovascularization, Physiologic; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-yes; Proto-Oncogene Proteins pp60(c-src) - physiology; Src kinase; src-Family Kinases - physiology; vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; yes protein
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(00)80221-X

Src kinase activity was found to protect endothelial cells from apoptosis during 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. Although mice lacking individual Src family kinases (SFKs) showed normal angiogenesis, mice deficient in pp60 c-src or pp62 c-yes showed no VEGF-induced vascular permeability (VP), yet fyn −/− mice displayed normal VP. In contrast, inflammation-mediated VP appeared normal in Src-deficient mice. Therefore, VEGF-, but not bFGF-, mediated angiogenesis requires SFK activity in general, whereas the VP activity of VEGF specifically depends on the SFKs, Src, or Yes.