Journal of Biological Chemistry
Volume 278, Issue 31, 1 August 2003, Pages 28743-28749
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Mechanisms of Signal Transduction
Receptor-dependent RhoA Activation in G12/G13-deficient Cells: GENETIC EVIDENCE FOR AN INVOLVEMENT OF Gq/G11*

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The small GTPase RhoA is involved in the regulation of various cellular functions like the remodeling of the actin cytoskeleton and the induction of transcriptional activity. G-protein-coupled receptors (GPCRs), which are able to activate Gq/G11 and G12/G13 are major upstream regulators of RhoA activity, and G12/G13 have been shown to couple GPCRs to the activation of Rho by regulating the activity of a subfamily of RhoGEF proteins. However, the possible contribution of Gq/G11 to the regulation of RhoA activity via GPCRs is controversial. We have used a genetic approach to study the role of heterotrimeric G-proteins in the activation of RhoA via endogenous GPCRs. In pertussis toxin-treated Gα12/Gα13-deficient as well as in Gαq/Gα11-deficient mouse embryonic fibroblasts (MEFs), in which coupling of receptors is restricted to Gq/G11 and G12/G13, respectively, receptor activation results in Rho activation. Rho activation induced by receptor agonists via Gq/G11 occurs with lower potency than Rho activation via G12/G13. Activation of RhoA via Gq/G11 is not affected by the phospholipase-C blocker U73122 or the Ca2+-chelator BAPTA, but can be blocked by a dominant-negative mutant of the RhoGEF protein LARG. Our data clearly show that G12/G13 as well as Gq/G11 alone can couple GPCRs to the rapid activation of RhoA. Gq/G11-mediated RhoA activation occurs independently of phospholipase C-β and appears to involve LARG.

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This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.