Mechanisms of focal adhesion kinase regulation

被引:110
作者
Cohen, LA [1 ]
Guan, JL [1 ]
机构
[1] Cornell Univ, Dept Mol Med, Ithaca, NY 14853 USA
关键词
D O I
10.2174/156800905774932798
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Focal adhesion kinase (FAK) is a tyrosine kinase whose phosphorylation state and activity is tightly linked to cell adhesion to the extracellular matrix through integrin receptors. FAK's regulation by adhesion places it in a key position to be able to influence cellular events that are either dependent on cell adhesion like cell proliferation and survival, or that require modulation of cell adhesion like cell migration. FAK's involvement in cellular pathways that regulate cell growth and cell movement suggests that it may contribute to the development of cancer or other diseases. FAK's possible involvement in these pathways makes it a potential drug target. In this review we will focus on the developing view how FAK's activity and phosphorylation are regulated within the cell. Specifically, we will address the contribution of integrins and growth factor dependent pathways to FAK's activation. The role of the tyrosine kinase Src in FAK's regulation will be discussed. The contribution of various negative regulators of FAK's phosphorylation on its regulation including phosphatases and proteases will be discussed. Lastly, the emerging role of FAK's amino terminal FERM like domain in FAK's regulation will be explored. FAK's function within a cell are tightly linked to its phosphorylation state, thus understanding its normal regulation in the cell will provide important insight into drug development by highlighting novel regulatory mechanisms within FAK that potentially may be exploited.
引用
收藏
页码:629 / 643
页数:15
相关论文
共 101 条
[41]   IDENTIFICATION OF SEQUENCES REQUIRED FOR THE EFFICIENT LOCALIZATION OF THE FOCAL ADHESION KINASE, PP125(FAK), TO CELLULAR FOCAL ADHESIONS [J].
HILDEBRAND, JD ;
SCHALLER, MD ;
PARSONS, JT .
JOURNAL OF CELL BIOLOGY, 1993, 123 (04) :993-1005
[42]   INTEGRINS - VERSATILITY, MODULATION, AND SIGNALING IN CELL-ADHESION [J].
HYNES, RO .
CELL, 1992, 69 (01) :11-25
[43]   ASSOCIATION OF THE AMINO-TERMINAL HALF OF C-SRC WITH FOCAL ADHESIONS ALTERS THEIR PROPERTIES AND IS REGULATED BY PHOSPHORYLATION OF TYROSINE-527 [J].
KAPLAN, KB ;
BIBBINS, KB ;
SWEDLOW, JR ;
ARNAUD, M ;
MORGAN, DO ;
VARMUS, HE .
EMBO JOURNAL, 1994, 13 (20) :4745-4756
[44]   C-SRC ENHANCES THE SPREADING OF SRC-/-FIBROBLASTS ON FIBRONECTIN BY A KINASE-INDEPENDENT MECHANISM [J].
KAPLAN, KB ;
SWEDLOW, JR ;
MORGAN, DO ;
VARMUS, HE .
GENES & DEVELOPMENT, 1995, 9 (12) :1505-1517
[45]   Direct transmembrane clustering and cytoplasmic dimerization of focal adhesion kinase initiates its tyrosine phosphorylation [J].
Katz, BZ ;
Miyamoto, S ;
Teramoto, H ;
Zohar, M ;
Krylov, D ;
Vinson, C ;
Gutkind, JS ;
Yamada, KM .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2002, 1592 (02) :141-152
[46]   Src family kinases are required for integrin but not PDGFR signal transduction [J].
Klinghoffer, RA ;
Sachsenmaier, C ;
Cooper, JA ;
Soriano, P .
EMBO JOURNAL, 1999, 18 (09) :2459-2471
[47]   SIGNAL TRANSDUCTION BY INTEGRINS - INCREASED PROTEIN TYROSINE PHOSPHORYLATION CAUSED BY CLUSTERING OF BETA-1 INTEGRINS [J].
KORNBERG, LJ ;
EARP, HS ;
TURNER, CE ;
PROCKOP, C ;
JULIANO, RL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (19) :8392-8396
[48]   Specific SHP-2 partitioning in raft domains triggers integrin-mediated signaling via Rho activation [J].
Lacalle, RA ;
Mira, E ;
Gómez-Moutón, C ;
Jiménez-Baranda, S ;
Martínez-A, C ;
Mañes, S .
JOURNAL OF CELL BIOLOGY, 2002, 157 (02) :277-289
[49]   SINGLE SUBUNIT CHIMERIC INTEGRINS AS MIMICS AND INHIBITORS OF ENDOGENOUS INTEGRIN FUNCTIONS IN RECEPTOR LOCALIZATION, CELL SPREADING AND MIGRATION, AND MATRIX ASSEMBLY [J].
LAFLAMME, SE ;
THOMAS, LA ;
YAMADA, SS ;
YAMADA, KM .
JOURNAL OF CELL BIOLOGY, 1994, 126 (05) :1287-1298
[50]   Tyr-863 phosphorylation enhances focal adhesion kinase autophosphorylation at Tyr-397 [J].
Leu, TH ;
Maa, MC .
ONCOGENE, 2002, 21 (46) :6992-7000