Direct Stimulation of the Guanine Nucleotide Exchange Activity of p115 RhoGEF by Gα 13

Abstract

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 α subunits, Gα 12 and Gα 13 , are stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF. Activated Gα 13 bound tightly to p115 RhoGEF and stimulated its capacity to catalyze nucleotide exchange on Rho. In contrast, activated Gα 12 inhibited stimulation by Gα 13 . Thus, p115 RhoGEF can directly link heterotrimeric G protein α subunits to regulation of Rho.