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

Abstract

Recent reports have shown that several heterotrimeric protein-coupled receptors that signal through Gαq 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 Gαq expressed in COS-7 cells coprecipitates with-the Rho guanine nucleotide exchange factor (GEF) Lbc. Furthermore, Gαq expression enhances Rho-dependent responses. Coexpressed Gαq 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 Gαq and Rho GEFs. The synergistic effect of Gαq on this response is inhibited by C3 exoenzyme and requires phospholipase C activation. Surprisingly, expression of Gαq, in contrast to that of Gα12 and Gα13, does not increase the amount of activated Rho. We also observe that Gαq enhances SRE.L stimulation by activated Rho, indicating that the effect of Gαq occurs downstream of Rho activation. Thus, Gαq 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 Gαq-generated signals enhance responses downstream of Rho activation.