Involvement of the small GTPase rho in integrin-mediated activation of mitogen-activated protein kinase.
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.
Renshaw
M W
MW
The Scripps Research Institute, Department of Vascular Biology, La Jolla, California 92037, USA.
Toksoz
D
D
Schwartz
M A
MA
D054758:A Kinase Anchor Proteins; D036002:ADP Ribose Transferases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001905:Botulinum Toxins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002411:Cation Exchange Resins / Q000494:pharmacology; D002448:Cell Adhesion; D002460:Cell Line; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D008055:Lipids / Q000494:pharmacology; D015778:Minor Histocompatibility Antigens; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D020741:rho GTP-Binding Proteins
D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002411:Cation Exchange Resins; D005353:Fibronectins; D016023:Integrins; D008055:Lipids; C086724:Lipofectamine; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate