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, Gα12 and Gα13, are stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF. Activated Gα13 bound tightly to p115 RhoGEF and stimulated its capacity to catalyze nucleotide exchange on Rho. In contrast, activated Gα12 inhibited stimulation by Gα13. Thus, p115 RhoGEF can directly link heterotrimeric G protein α subunits to regulation of Rho.
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