Open Access
Article
Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility
Steven K Hanks1,Larisa Ryzhova1,Nah-Young Shin1,Jan Brábek1
1
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. steve.hanks@vanderbilt.edu
DOI: 10.2741/1114 Volume 8 Issue 4, pp.982-996
Published: 01 May 2003
(This article belongs to the Special Issue FAK family kinases in disease)
Abstract

Focal adhesion kinase (FAK) was first described in 1992 as a novel nonreceptor protein-tyrosine kinase localized prominently within focal adhesions, suggesting a signaling role in regulating cell behavior resulting from integrin interaction with the extracellular matrix. Subsequent studies over the past decade have established functional roles for FAK as a positive regulator of both cell motility and cell survival, while providing considerable insight into signaling mechanisms involved. FAK signaling results from its ability to become highly phosphorylated in response to integrin-mediated adhesion on Tyr-397, permitting interactions with a number of different signaling effectors containing Src homology 2 (SH2) domains. Src-family kinases recruited to the Tyr-397 site phosphorylate two FAK-interacting proteins, Crk-associated substrate (CAS) and paxillin, which results ultimately in regulation of Rho-family GTPases contributing to cell motility. CAS phosphorylation, as well as phosphatidylinositol 3-kinase (PI3K) activation resulting from its binding to the FAK Tyr-397 site, have been implicated as downstream FAK signaling events that confer a resistance to apoptosis. This article reviews these and other aspects of FAK signaling and function.

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Steven K Hanks, Larisa Ryzhova, Nah-Young Shin, Jan Brábek. Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility. Frontiers in Bioscience-Landmark. 2003. 8(4); 982-996.