p115 RhoGEF, a GTPase Activating Protein for Gα ₁₂ and Gα ₁₃

Abstract

Members of the regulators of G protein signaling (RGS) family stimulate the intrinsic guanosine triphosphatase (GTPase) activity of the alpha subunits of certain heterotrimeric guanine nucleotide-binding proteins (G proteins). The guanine nucleotide exchange factor (GEF) for Rho, p115 RhoGEF, has an amino-terminal region with similarity to RGS proteins. Recombinant p115 RhoGEF and a fusion protein containing the amino terminus of p115 had specific activity as GTPase activating proteins toward the alpha subunits of the G proteins G12 and G13, but not toward members of the Gs, Gi, or Gq subfamilies of Galpha proteins. This GEF may act as an intermediary in the regulation of Rho proteins by G13 and G12.

Role of G protein-coupled receptors in inflammation

“…The selectivity for activation of these G proteins depends on the agonists that bind to the receptor [61] . In endothelial cells, thrombin binding to PAR1 leads to activation of p115 RhoGEF, which provides a functional link between G13 and RhoA [62] . Activation of RhoA is responsible for stress fiber formation, and increased calcium flux triggers other signaling pathways which ultimately lead to myosin light chain-dependent contraction of endothelial cells [63] .…”

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.…”

Signaling mechanisms for regulation of chemotaxis

“…We recently added PAK1 to the list by demonstrating the interaction between Gβγ and PAK1, which is involved in chemoattractant-mediated activation of Cdc42 and PAK1 [10]. Chemoattractants can also couple to G16 [11] and probably G12/13 [12], which have been shown to activate small GTPase RhoA via a guanine nucleotide exchange factor (GEF) 115 [13][14][15]. In the past ten years, many of the chemoattractant signaling pathways were comprehensively characterizing using a combination of biochemical, molecular and cell biological, and transgenic approaches.…”