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

doi:10.1128/MCB.20.15.5758-5765.2000

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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 integrinsto mediate directed cell migration. In this study, $beta$ 1-dependentcell spreading was found to be delayed in GD25 cells expressing $beta$ 1A_Y783/795F compared to that in wild-type GD25- $beta$ 1A. Focal adhesionkinase (FAK) tyrosine phosphorylation and activation were severelyimpaired in response to $beta$ 1-dependent adhesion in GD25- $beta$ 1A_Y783/795Fcells compared to that in wild-type GD25- $beta$ 1A or mutants in whichonly a single tyrosine was altered ( $beta$ 1A_Y783F or $beta$ 1A_Y795F). Phosphorylationsite-specific antibodies selective for FAK phosphotyrosine 397indicated that the defect in FAK phosphorylation via $beta$ 1A_Y783/795Flies at the level of the initial autophosphorylation step. Indeed, $beta$ 1A-dependent tyrosine phosphorylation of tensin and paxillinwas lost in the $beta$ 1A_Y783/795F cells, consistent with the impairmentin FAK activation. In contrast, p130^CAS overall tyrosine phosphorylation was unaffected by the $beta$ 1 mutations.Despite the defect in $beta$ 1-mediated FAK activation, FAK was stilllocalized to focal adhesions. Taken together, the phenotype ofthe GD25- $beta$ 1A_Y783/795F cells resembles, but is distinct from, thephenotype observed in FAK-null cells. These observations arguethat tyrosines 783 and 795 within the cytoplasmic tail of integrinsubunit $beta$ 1A are critical mediators of FAK activation and cellspreading in GD25cells.

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

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