Physical and Functional Interactions of Gα_q with Rho and Its Exchange Factors

Recent reports have shown that several heterotrimeric protein-coupled receptors that signal through Gα_q can induce Rho-dependent responses, but the pathways that mediate the interaction between Gα _q and Rho have not yet been identified. In this report we present evidence that Gα_q expressed in COS-7 cells coprecipitates with-the Rho guanine nucleotide exchange factor (GEF) Lbc. Furthermore, Gα_q expression enhances Rho-dependent responses. Coexpressed Gα_q and Lbc have a synergistic effect on the Rho-dependent rounding of 1321N1 astrocytoma cells. In addition, serum response factor-dependent gene expression, as assessed by the SRE.L reporter gene, is synergistically activated by Gα_q and Rho GEFs. The synergistic effect of Gα_q on this response is inhibited by C3 exoenzyme and requires phospholipase C activation. Surprisingly, expression of Gα_q, in contrast to that of Gα₁₂ and Gα₁₃, does not increase the amount of activated Rho. We also observe that Gα_q enhances SRE.L stimulation by activated Rho, indicating that the effect of Gα_q occurs downstream of Rho activation. Thus, Gα_q interacts physically and/or functionally with Rho GEFs; however this does not appear to lead to or result from increased activation of Rho. We suggest that Gα_q-generated signals enhance responses downstream of Rho activation.