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Originally published In Press as doi:10.1074/jbc.M208607200 on October 19, 2002

J. Biol. Chem., Vol. 278, Issue 3, 1975-1985, January 17, 2003
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ERK1 Associates with alpha vbeta 3 Integrin and Regulates Cell Spreading on Vitronectin*

Marnie S. RobertsDagger , Alison J. WoodsDagger , Peter E. Shaw§, and Jim C. NormanDagger

From the Dagger  Department of Biochemistry, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom and the § School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, United Kingdom

Kinases that associate with integrins are likely to mediate the assembly/disassembly of cell:matrix junctions during cell migration. Here we show that ERK1 associates with alpha vbeta 3 integrin following the addition of platelet-derived growth factor to serum-starved Swiss or NIH 3T3 fibroblasts in an interaction that is mediated by the central region of the beta 3 integrin cytodomain. alpha vbeta 3·ERK1 association occurred prior to focal complex formation and was seen to initiate in small punctate complexes primarily in the peripheral regions of the plasma membrane. Expression of a dominant negative mutant of ERK1 (but not ERK2) significantly reduced the spreading of cells on vitronectin, whereas cell spreading on fibronectin was unaffected by inhibition of ERK1. In contrast, inhibition of ERK activation by PD98059 had no effect on the platelet-derived growth factor-regulated Rab4-dependent flux of alpha vbeta 3 integrin from early endosomes to the plasma membrane, an event that is also necessary for cells to spread efficiently on vitronectin. We propose that alpha vbeta 3 integrin must recycle to the plasma membrane via the Rab4 pathway and recruit active ERK1 in order to function efficiently.

* This work was generously supported by grants from the Wellcome Trust.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Holder of a Wellcome Trust Career Development Fellowship. To whom correspondence should be addressed. Tel.: 0116-252-5250; Fax: 0116-252-3369; E-mail: jcn2@le.ac.uk.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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