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Published 1 April 2002. doi:10.1083/jcb.200109079
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© The Rockefeller University Press, 0021-9525/2002/4/149 $5.00
The Journal of Cell Biology, Volume 157, Number 1, April 1, 2002 149-160

Article

 Src-mediated coupling of focal adhesion kinase to integrin {alpha}vß5 in vascular endothelial growth factor signaling

Brian P. Eliceiri1, Xose S. Puente1, John D. Hood1, Dwayne G. Stupack1, David D. Schlaepfer1, Xiaozhu Z. Huang2, Dean Sheppard2 and David A. Cheresh1

1 Departments of Immunology and Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037
2 Lung Biology Center, University of California San Francisco, San Francisco, CA 94143

Address correspondence to Brian P. Eliceiri, IMM-24, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: (858) 784-9317. Fax: (858) 784-8926. E-mail: eliceiri{at}scripps.edu

Vascular endothelial growth factor (VEGF) promotes vascular permeability (VP) and neovascularization, and is required for development. We find that VEGF-stimulated Src activity in chick embryo blood vessels induces the coupling of focal adhesion kinase (FAK) to integrin {alpha}vß5, a critical event in VEGF-mediated signaling and biological responsiveness. In contrast, FAK is constitutively associated with ß1 and ß3 integrins in the presence or absence of growth factors. In cultured endothelial cells, VEGF, but not basic fibroblast growth factor, promotes the Src-mediated phosphorylation of FAK on tyrosine 861, which contributes to the formation of a FAK/{alpha}vß5 signaling complex. Moreover, formation of this FAK/{alpha}vß5 complex is significantly reduced in pp60c-src-deficient mice. Supporting these results, mice deficient in either pp60c-src or integrin ß5, but not integrin ß3, have a reduced VP response to VEGF. This FAK/{alpha}vß5 complex was also detected in epidermal growth factor-stimulated epithelial cells, suggesting a function for this complex outside the endothelium. Our findings indicate that Src can coordinate specific growth factor and extracellular matrix inputs by recruiting integrin {alpha}vß5 into a FAK-containing signaling complex during growth factor–mediated biological responses.

Key Words: VEGF; vascular permeability; Src; tyrosine kinase; integrin


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