JCB logo
Quantitative Colocalization Analysis Software
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 1 April 2002. doi:10.1083/jcb.200109079
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 580K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Eliceiri, B. P.
Right arrow Articles by Cheresh, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eliceiri, B. P.
Right arrow Articles by Cheresh, D. A.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*Protein
*UniGene
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*L-TYROSINE
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© 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


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents