Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Gα13

Signaling pathways that link extracellular factors to activation of the monomeric guanosine triphosphatase (GTPase) Rho control cytoskeletal rearrangements and cell growth. Heterotrimeric guanine nucleotide-binding proteins (G proteins) participate in several of these pathways, although their mechanisms are unclear. The GTPase activities of two G protein alpha subunits, G alpha(12 )and G alpha(13), are stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF. Activated G alpha(13) bound tightly to p115 RhoGEF and stimulated its capacity to catalyze nucleotide exchange on Rho, In contrast, activated G alpha(12) inhibited stimulation by G alpha(13). Thus, p115 RhoGEF can directly link heterotrimeric G protein a subunits to regulation of Rho.