Document Type

Article

Version Deposited

Published Version

Publication Date

11-21-2003

Publication Title

Journal of Biological Chemistry

DOI

10.1074/jbc.M307526200

Abstract

Cas is a member of the focal adhesion complex. Phosphorylation of Cas by Src is an important event leading to cell transformation. Using mass spectrometry, we have mapped 11 sites in Cas that are phosphorylated by Src. These sites are all located between residues 132 and 414 of Cas, in a region that is required for binding to a number of other proteins including Crk. We tested synthetic peptides modeled on Cas phosphorylation sites, and found that the sequence containing tyrosine 253 was phosphorylated by Src most efficiently. Using cells derived from Cas-deficient mice, we confirmed that Cas greatly enhanced the ability of Src to transform cells. Phosphorylation of Cas on tyrosine 253 was not required for Src to increase growth rate, suppress contact inhibition, or suppress anchorage dependence. Yet, in contrast to these growth characteristics, phosphorylation of Cas on tyrosine 253 was required for Src to promote cell migration. Thus, a single phosphorylation site on this focal adhesion adaptor protein can effectively separate cell migration from other transformed growth characteristics.

Comments

American Society of Biochemistry and Molecular Biology

Permitted :

- to post the accepted manuscript version of the work, the “Paper in Press,” on the author’s personal web page, their personal or institutional repository, or their funding body’s archive or designated noncommercial repository, provided that a link to the article in the journal

- post the final edited PDFs, created by ASBMB, to their own departmental/university websites, provided that the posting does not happen until 12 months after publication, and that a link to the article in the journal is included.

Published Citation

Goldberg GS, Alexander DB, Pellicena P, Zhang ZY, Tsuda H, Miller WT. Src phosphorylates Cas on tyrosine 253 to promote migration of transformed cells. J Biol Chem. 2003 Nov 21;278(47):46533-40. Epub 2003 Sep 11. doi: 10.1074/jbc.M307526200. PMID: 12972425. PMCID: PMC2441571.

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