A mechanism for regulation of the adhesion-associated proteintyrosine kinase pp125FAK

Nature
A Richardson, T Parsons

Abstract

Focal adhesion kinase (pp125FAK) is a member of a growing family of structurally distinct protein tyrosine kinases that includes the recently identified FakB and PYK2/CAKbeta/RAFTK. Activation of pp125FAK has been functionally linked to the formation of focal adhesions, integrin-mediated sites of contact between the cell and the extracellular matrix. The carboxy-terminal domain of pp125FAK is also expressed as a separate protein called pp41/43FRNK (where FRNK represents pp125FAK-related non-kinase). Here we show that pp41/43FRNK acts as an inhibitor of pp125FAK by transiently blocking the formation of focal adhesions on fibronectin and constitutively reducing tyrosine phosphorylation of both pp125FAK and two focal adhesion proteins, tensin and paxillin. These inhibitory effects of pp41/43FRNK are reversed by co-expression of pp125FAK, suggesting that pp125FAK and pp41/43 FRNK compete for a common binding protein(s) whose association with pp125FAK is necessary for signalling by pp125FAK. We propose that pp41/43FRNK functions as an endogenous regulator of pp125FAK, thus providing an unusual means to regulate both tyrosine kinase activity and cellular adhesion to the extracellular matrix.

References

Sep 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S K HanksS K Patel
Jun 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M D SchallerJ T Parsons
May 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S B KannerJ T Parsons
Mar 1, 1994·Molecular and Cellular Biology·M D SchallerJ T Parsons
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·S B KannerP Y Chan
May 1, 1995·Molecular and Cellular Biology·M D Schaller, J T Parsons
Mar 1, 1995·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A Richardson, J T Parsons
Oct 1, 1994·Current Opinion in Cell Biology·M D Schaller, J T Parsons
Jan 15, 1993·Biochemical and Biophysical Research Communications·E André, M Becker-André

❮ Previous
Next ❯

Citations

Dec 19, 1998·Microscopy Research and Technique·J A Greenwood, J E Murphy-Ullrich
Oct 3, 1999·Microscopy Research and Technique·P DefilippiG Tarone
Jul 27, 1999·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C M Sorenson, N Sheibani
Nov 17, 1998·Archives of Insect Biochemistry and Physiology·M J Lee, G J Goldsworthy
Oct 12, 2000·Biochemical and Biophysical Research Communications·M Lobo, I Zachary
Jan 23, 2008·Archives of Dermatological Research·Si-Yuan ChenMasutaka Furue
Jan 27, 2009·Cancer Metastasis Reviews·Jihe Zhao, Jun-Lin Guan
Nov 1, 2011·Cancer Metastasis Reviews·Daniel J Hermanson, Lawrence J Marnett
Dec 2, 2005·Clinical & Experimental Metastasis·Masuo HanadaYukihide Iwamoto
May 27, 2004·Gene Expression Patterns : GEP·María Guadalupe GarcíaMerrill B Hille
Jun 4, 1999·Progress in Biophysics and Molecular Biology·D D SchlaepferD J Sieg
May 1, 1997·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·M ImaizumiM Hamaguchi
Oct 1, 1996·Current Opinion in Cell Biology·S Dedhar, G E Hannigan
Aug 26, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·R J JonesM C Frame
Apr 12, 2003·Surgical Oncology·Rolf J CravenWilliam G Cance
Aug 8, 1998·Trends in Cell Biology·D D Schlaepfer, T Hunter
Aug 8, 1998·Trends in Cell Biology·P KeelyR Juliano
May 6, 2003·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Moulay A Alaoui-Jamali, He Qiang
Aug 31, 2002·Biomolecular Engineering·P Linez-BataillonH F Hildebrand
Apr 30, 2005·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Amy L LarkWilliam Cance
Aug 3, 2005·Nature Reviews. Cancer·Gordon W McLeanMargaret C Frame
Nov 7, 2001·The Biochemical Journal·M D Schaller, E M Schaefer
Dec 17, 2003·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·H-S MoonS-C Kim
Apr 7, 2010·Proceedings of the National Academy of Sciences of the United States of America·Massimiliano StagiThomas Biederer
Dec 10, 1999·The Journal of Biological Chemistry·R H PalmerT Hunter
Mar 27, 2012·The Journal of Biological Chemistry·Melissa A KacenaAngela Bruzzaniti

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.