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Open Access Research article

Cbl-associated protein is tyrosine phosphorylated by c-Abl and c-Src kinases

Inga Fernow12, Ana Tomasovic12, Ann Siehoff-Icking2 and Ritva Tikkanen12*

Author Affiliations

1 Institute of Biochemistry, University of Giessen, Friedrichstrasse 24, 35392 Giessen, Germany

2 Institute of Biochemistry II, University Clinic of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany

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BMC Cell Biology 2009, 10:80  doi:10.1186/1471-2121-10-80

Published: 5 November 2009

Abstract

Background

The c-Cbl-associated protein (CAP), also known as ponsin, localizes to focal adhesions and stress fibers and is involved in signaling events. Phosphorylation has been described for the other two members of the sorbin homology family, vinexin and ArgBP2, but no data exist about the putative phosphorylation of CAP. According to previous findings, CAP binds to tyrosine kinase c-Abl. However, it is not known if CAP is a substrate of c-Abl or other tyrosine kinases or if phosphorylation regulates its localization.

Results

We here show that CAP is Tyr phosphorylated by and interacts with both c-Abl and c-Src. One major phosphorylation site, Tyr360, and two minor contributors Tyr326 and Tyr632 were identified as Abl phosphorylation sites, whereas Src preferentially phosphorylates Tyr326 and Tyr360. Phosphorylation of CAP was not necessary for its localization to focal adhesions and stress fibers, but Tyr326Phe substitution alters the function of CAP during cell spreading.

Conclusion

This is the first demonstration of phosphorylation of CAP by any kinase. Our findings suggest that coordinated action of Src and Abl might regulate the function of CAP and reveal a functional role especially for the Src-mediated Tyr phosphorylation of CAP in cell spreading.