Document Type

Article

Version Deposited

None (link only)

Publication Date

7-28-2006

Publication Title

Journal of Biological Chemistry

DOI

10.1074/jbc.M602311200

Abstract

Cas is a multidomain signaling protein that resides in focal adhesions. Cas possesses a large central substrate domain containing 15 repeats of the sequence YXXP, which are phosphorylated by Src. The phosphorylation sites are essential for the roles of Cas in cell migration and in regulation of the actin cytoskeleton. We showed previously that Src catalyzes the multisite phosphorylation of Cas via a processive mechanism. In this study, we created mutant forms of Cas to identify the determinants for processive phosphorylation. Mutants containing single or multiple YXXP mutations were phosphorylated processively by Src, suggesting that individual sites are dispensable. The results also suggest that there is no defined order to the Cas phosphorylation events. We also studied the effects of these mutations by reintroducing Cas into Cas-deficient fibroblasts. Mutants lacking some or all YXXP sites augment the ability of Src to promote anchorage-independent growth. On the other hand, deletion of YXXP sites compromises the ability of Cas to promote tumor cell migration.

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.


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