DIRECT STIMULATION OF THE GUANINE-NUCLEOTIDE EXCHANGE ACTIVITY OF P115 RHOGEF BY G-ALPHA(13)

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