Physical and functional interactions of Gαq with Rho and its exchange factors

Recent reports have shown that several heterotrimeric protein-coupled receptors that signal through G alpha (q) can induce Rho dependent responses, but the pathways that mediate the interaction between G alpha (q) and Rho have not yet been identified. In this report we present evidence that G alpha (q) expressed in COS-7 cells coprecipitates with the Rho guanine nucleotide exchange factor (GEF) Lbc, Furthermore, G alpha (q) expression enhances Rho-dependent responses. Coexpressed G alpha (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 G alpha (q) and Rho GEFs. The synergistic effect of G alpha (q) on this response is inhibited by C3 exoenzyme and requires phiospholipase C activation. Surprisingly, expression of G alpha (q), in contrast to that of G alpha (12) and G alpha (13), does not increase the amount of activated Rho. We also observe that G alpha (q) enhances SRE.L stimulation by activated Rho, indicating that the effect of G alpha (q) occurs downstream of Rho activation. Thus, G alpha (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 G alpha (q)-generated signals enhance responses downstream of Rho activation.