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Molecular and Cellular Biology, August 2000, p. 5758-5765, Vol. 20, No. 15
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Cytoplasmic Tyrosines of Integrin Subunit beta 1 Are Involved in Focal Adhesion Kinase Activation

Krister Wennerberg,1,* Annika Armulik,1 Takao Sakai,2,3 Marjam Karlsson,1 Reinhard Fässler,3 Erik M. Schaefer,4 Deane F. Mosher,2 and Staffan Johansson1

Department of Medical Biochemistry and Microbiology, Uppsala University, S-751 23 Uppsala,1 and Department of Experimental Pathology, Lund University, S-221 85 Lund,3 Sweden; Departments of Medicine and Biomolecular Chemistry, University of Wisconsin---Madison, Madison, Wisconsin 537062; and Signal Transduction and Immunology, QCB, BioSource International, Hopkinton, Massachusetts 017484

Received 4 January 2000/Returned for modification 2 February 2000/Accepted 1 May 2000

We have previously shown that mutation of the two tyrosines in the cytoplasmic domain of integrin subunit beta 1 (Y783 and Y795) to phenylalanines markedly reduces the capability of beta 1A integrins to mediate directed cell migration. In this study, beta 1-dependent cell spreading was found to be delayed in GD25 cells expressing beta 1AY783/795F compared to that in wild-type GD25-beta 1A. Focal adhesion kinase (FAK) tyrosine phosphorylation and activation were severely impaired in response to beta 1-dependent adhesion in GD25-beta 1AY783/795F cells compared to that in wild-type GD25-beta 1A or mutants in which only a single tyrosine was altered (beta 1AY783F or beta 1AY795F). Phosphorylation site-specific antibodies selective for FAK phosphotyrosine 397 indicated that the defect in FAK phosphorylation via beta 1AY783/795F lies at the level of the initial autophosphorylation step. Indeed, beta 1A-dependent tyrosine phosphorylation of tensin and paxillin was lost in the beta 1AY783/795F cells, consistent with the impairment in FAK activation. In contrast, p130CAS overall tyrosine phosphorylation was unaffected by the beta 1 mutations. Despite the defect in beta 1-mediated FAK activation, FAK was still localized to focal adhesions. Taken together, the phenotype of the GD25-beta 1AY783/795F cells resembles, but is distinct from, the phenotype observed in FAK-null cells. These observations argue that tyrosines 783 and 795 within the cytoplasmic tail of integrin subunit beta 1A are critical mediators of FAK activation and cell spreading in GD25 cells.

* Corresponding author. Present address: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 962-1057. Fax: (919) 966-0162. E-mail: krister{at}med.unc.edu.

Molecular and Cellular Biology, August 2000, p. 5758-5765, Vol. 20, No. 15
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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