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 alpha subunits, Galpha12 and Galpha13, are stimulated by the Rho guanine nucleotide exchange factor p115 RhoGEF. Activated Galpha13 bound tightly to p115 RhoGEF and stimulated its capacity to catalyze nucleotide exchange on Rho. In contrast, activated Galpha12 inhibited stimulation by Galpha13. Thus, p115 RhoGEF can directly link heterotrimeric G protein alpha subunits to regulation of Rho.

Cell fusion promotes chemoresistance in metastatic colon carcinoma

“…The ectopic expression of N19RhoA has been demonstrated to inhibit endogenous Rho function and the Ga13-RhoA pathway by forming non-productive complexes with guanine nucleotide exchange factors (GEFs) for Rho. 27 The ectopic expression of N19RhoA significantly reduced the percentage of fused CT26 cells whereas the expression of control acGFP1 vector had no effect (Figure 6f). …”

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

“…It was reported that P2Y 6 receptor coupled with Gα 12/13 signaling in cardiomyocytes [23] and human umbilical vein endothelial cells, phosphorylation of VASP was mediated by Gα 13 [19] and Rho activation was mediated by Gα 12/13 signals [34][35][36]. It has been established that Rho activation regulates cytoskeletal arrangements [37].…”

Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase

“…There is a small subfamily of Dbl RhoGEFs whose members bind and serve as effectors for heterotrimeric G-protein a-subunits. This subfamily of RhoGEFs consists of Lsc/p115 RhoGEF (Glaven et al, 1996;Hart et al, 1996Hart et al, , 1998Whitehead et al, 1996;Kozasa et al, 1998), PDZ-RhoGEF (Rholike GEF containing a PDZ (PSD-95/Disc-large/ZO-1) domain/GTRAP-48 (Fukuhara et al, 1999), and leukemia-associated RhoGEF (LARG) (Fukuhara et al, 2000;Reuther et al, 2001). These RhoGEFs can bind Ga 12/13 through a regulator of G-protein signaling (RGS)-like domain in their N-terminus.…”