Tyrosine Phosphorylation of p130Cas and Cortactin Accompanies Integrin-mediated Cell Adhesion to Extracellular Matrix

doi:10.1074/jbc.270.38.22259

Tyrosine Phosphorylation of p130^Cas and Cortactin Accompanies Integrin-mediated Cell Adhesion to Extracellular Matrix (*)

From the Cancer Research Center, La Jolla Cancer Research Foundation, La Jolla, California 92037

^¶ To whom correspondence should be addressed:
Cancer Research Center, La Jolla Cancer Research Foundation, 10901 N. Torrey Pines Road, La Jolla, CA 92037.
Tel.: 619-455-6480; Fax: 619-455-0452; ruoslahti{at}ljcrf.edu

Abstract

We show in this report that two v-src substrate proteins, p130 and cortactin, become tyrosine-phosphorylated during integrin-mediated cell adhesion to extracellular matrix substrata and upon cell attachment onto immobilized anti-integrin antibodies. This tyrosine phosphorylation does not occur when cells attach to polylysine or through antibodies against major histocompatibility complex. It also does not take place when adhesion-mediated reorganization of the actin cytoskeleton is inhibited with cytochalasin D. Tyrosine phosphorylation of p130 and cortactin coincides with tyrosine phosphorylation of focal adhesion kinase during integrin-mediated cell adhesion but is independent of cell adhesion in v-src-transformed cells. The tyrosine-phosphorylated sites in p130 and cortactin may serve as binding sites for proteins containing Src homology 2 domains, as is the case with two other integrin-regulated docking proteins, focal adhesion kinase and paxillin. Thus, these results suggest that ligand binding of integrins regulates the tyrosine phosphorylation state of multiple docking proteins. These proteins may mediate anchorage dependence of growth; their misregulation in v-src-transformed and other tumorigenic cells may be responsible for the anchorage independence of such cells.

Footnotes

↵^§ Supported by the Susan G. Komen Breast Cancer Foundation, the Academy of Finland, and the Emil Aaltonen Foundation.
↵* This work was supported in part by National Institutes of Health Grants CA 28896, CA 62042, CA 67224, and Cancer Center Support Grant CA 30199 (to E. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¹ The abbreviations used are:

ECM

extracellular matrix

FAK

focal adhesion kinase

SH

src homology

REF

rat embryo fibroblast

DMEM

Dulbecco's modified Eagle's medium

MHC

major histocompatibility complex.
- Received June 5, 1995.