Involvement of the Small GTPase Rho in Integrin-mediated Activation of Mitogen-activated Protein Kinase*
- 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
- ¶ To whom correspondence should be addressed. Tel.: 619-784-7140; Fax: 619-784-7360; E-mail: schwartz{at}scripps.edu.
Abstract
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.
Footnotes
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↵* This work was supported by United States Public Health Service Grant R01 GM47214 (to M. A. S.) and Training Grant HL07695 (to M. W. R.). 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.
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↵1 The abbreviations used are:
- MAP
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mitogen-activated protein
- DMEM
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Dulbecco's modified Eagle's medium
- BSA
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bovine serum albumin
- IP
-
immunoprecipitation
- TPA
-
12-O-tetradecanoylphorbol-13-acetate.
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- Received May 30, 1996.
- Revision received July 10, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
