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

Low molecular weight G proteins of the Rho subfamily are regulators of actin cytoskeletal organization. In contrast to the heterotrimeric G proteins, the small GTPases are not directly activated through Ligand binding to G protein-coupled receptors (GPCRs). However, a subset of GPCRs, including those for lysophosphatidic acid and thrombin, induce stress fibers, focal adhesions, and cell rounding through Rho-dependent pathways. C3 exoenzyme has been a useful tool for demonstrating Rho involvement in these and other responses, including Ca2+ sensitization of smooth muscle contraction, cell migration, transformation, and serum response element-mediated gene expression. Most of the GPCRs that induce Rho-dependent responses can activate G(q), but 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 bind and activate Rho-specific guanine nucleotide exchange factors, providing a mechanism by which GPCRs that couple to G alpha(12/13), could activate Rho and its downstream responses.