JCB logo
amgmicro.com
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 438K)
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 Cary, L. A.
Right arrow Articles by Guan, J.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cary, L. A.
Right arrow Articles by Guan, J.-L.
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, 0021-9525/1998//211 $5.00
The Journal of Cell Biology, Volume 140, Number 1, , 1998 211-221

Article

Identification of p130Cas as a Mediator of Focal Adhesion Kinase–promoted Cell Migration



Leslie A. Cary*, Dong Cho Han*, Thomas R. Polte{ddagger}, Steven K. Hanks{ddagger}, and Jun-Lin Guan*

* Cancer Biology Laboratories, Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853; and {ddagger} Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Previously we have demonstrated that focal adhesion kinase (FAK)-promoted migration on fibronectin (FN) by its overexpression in CHO cells is dependent on FAK autophosphorylation at Y397 and subsequent binding of Src to this site. In this report, we have examined the role of FAK association with Grb2 and p130Cas, two downstream events of the FAK/Src complex that could mediate integrin-stimulated activation of extracellular signal-regulated kinases (Erks). We show that a Y925F FAK mutant was able to promote cell migration as efficiently as FAK and that the transfected FAK demonstrated no detectable association with Grb2 in CHO cells. In contrast, cells expressing a FAK P712/715A mutant demonstrated a level of migration comparable to that of control cells. This mutation did not affect FAK kinase activity, autophosphorylation, or Src association but did significantly reduce p130Cas association with FAK. Furthermore, FAK expression in CHO cells increased tyrosine phosphorylation of p130Cas and its subsequent binding to several SH2 domains, which depended on both the p130Cas binding site and the Src binding site. However, we did not detect increased activation of Erks in cells expressing FAK, and the MEK inhibitor PD98059 did not decrease FAK-promoted cell migration. Finally, we show that coexpression of p130Cas further increased cell migration on FN and coexpression of the p130Cas SH3 domain alone functioned as a dominant negative mutant and decreased cell migration. Together, these results demonstrate that p130Cas, but not Grb2, is a mediator of FAK-promoted cell migration and suggest that FAK/ p130Cas complex targets downstream pathways other than Erks in mediating FAK-promoted cell migration.

Abbreviations used in this paper: CasSH3, SH3 domain of p130Cas; ECM, extracellular matrix; Erks, extracellular signal-regulated kinases; FAK, focal adhesion kinase; FN, fibronectin; GST, glutathione S-transferase; PI 3-kinase, phosphatidylinositol 3-kinase; SH2 and SH3, Src homology 2 and 3.

This research was supported by National Institutes of Health (NIH) grant GM48050 and The Council for Tobacco Research, USA, to J.-L. Guan, and NIH grant GM49882 to S. Hanks.

Address all correspondence to Jun-Lin Guan, Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. Tel.: (607) 253-3586. Fax: (607) 253-3708.

Thomas Polte's current address is Children's Hospital/Harvard Medical School, Department of Surgical Research, 300 Longwood Ave., Boston, MA 02115.


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