The role of Rho in G protein-coupled receptor signal transduction

Low molecular weight G proteins of the Rho subfamily are regulators of acti n cytoskeletal organization. In contrast to the heterotrimeric G proteins, the small GTPases are not directly activated through Ligand binding to G pr otein-coupled receptors (GPCRs). However, a subset of GPCRs, including thos e for lysophosphatidic acid and thrombin, induce stress fibers, focal adhes ions, and cell rounding through Rho-dependent pathways. C3 exoenzyme has be en a useful tool for demonstrating Rho involvement in these and other respo nses, including Ca2+ sensitization of smooth muscle contraction, cell migra tion, transformation, and serum response element-mediated gene expression. Most of the GPCRs that induce Rho-dependent responses can activate G(q), bu t this is not a sufficient signal. Recent data demonstrate that G alpha(12/ 13), can induce Rho-dependent responses. Furthermore, G alpha(12/13), can b ind and activate Rho-specific guanine nucleotide exchange factors, providin g a mechanism by which GPCRs that couple to G alpha(12/13), could activate Rho and its downstream responses.