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 αvβ5, a critical event in VEGF-mediated signaling and biological responsiveness. In contrast, FAK is constitutively associated with β1 and β3 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/αvβ5 signaling complex. Moreover, formation of this FAK/αvβ5 complex is significantly reduced in pp60c-src-deficient mice. Supporting these results, mice deficient in either pp60c-src or integrin β5, but not integrin β3, have a reduced VP response to VEGF. This FAK/αvβ5 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 αvβ5 into a FAK-containing signaling complex during growth factor–mediated biological responses.
Src-mediated coupling of focal adhesion kinase to integrin αvβ5 in vascular endothelial growth factor signaling
Abbreviations used in this paper: aa, amino acid(s); bFGF, basic FGF; CAM, chorioallantoic membrane; EB, Evan's Blue; FAK, focal adhesion kinase; GST, glutathione S-transferase; HA, hemagglutinin; HUVEC, human umbilical vein endothelial cell; MAP, mitogen-activated protein; SFK, Src family kinase; VEGF, vascular endothelial growth factor; VP, vascular permeability.
Brian P. Eliceiri, Xose S. Puente, John D. Hood, Dwayne G. Stupack, David D. Schlaepfer, Xiaozhu Z. Huang, Dean Sheppard, David A. Cheresh; Src-mediated coupling of focal adhesion kinase to integrin αvβ5 in vascular endothelial growth factor signaling . J Cell Biol 1 April 2002; 157 (1): 149–160. doi: https://doi.org/10.1083/jcb.200109079
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