Volume 271, Number 36, Issue of September 6, 1996 pp. 21691-21694
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Involvement of the Small GTPase Rho in Integrin-mediated Activation of Mitogen-activated Protein Kinase

(Received for publication, May 30, 1996, and in revised form, July 10, 1996)

Mark W. Renshaw , Deniz Toksoz ^§ and Martin Alexander Schwartz

From the  The Scripps Research Institute, Department of Vascular Biology, La Jolla, California 92037 and the ^§ Department of Physiology, Tufts Medical School, Department of Physiology, Boston, Massachusetts 02115

Engagement and clustering of integrins triggers a number of intracellular signaling events, including activation of the mitogen-activated protein (MAP) kinases Erk1 and Erk2. To investigate the mechanism by which integrins mediate the activation of MAP kinases upon binding of NIH 3T3 cells to fibronectin, we assessed the effects of both inhibiting and activating the small GTPase Rho. We observed that inhibition of Rho by the Rho-specific inhibitor C3 exoenzyme or by a dominant negative Rho A (RhoN19) inhibited MAP kinase activation. Conversely, activation of Rho by expression of an activated Rho A mutant (RhoQ63L), or the Rho-specific guanine nucleotide exchange factor lbc, enhanced and partially mimicked activation of Erk2 by plating on fibronectin. These results therefore show that Rho is involved in the integrin-dependent activation of MAP kinase.

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