Rho guanine nucleotide exchange factor 25 (ARHGEF25)

Rho guanine nucleotide exchange factor 25 (ARHGEF25), also known as GEFT or p63RhoGEF, is a member of the Rho guanine nucleotide exchange factors family that catalyzes the exchange of GDP for GTP on Rho GTPases, especially RhoA, in response to signals from Gαq/11-coupled receptors[1][2][4]. This activation leads to actin cytoskeleton reorganization, formation of stress fibers, and enhanced cellular contractility, particularly in vascular smooth muscle cells, contributing to Ca²⁺-sensitized force generation and blood pressure regulation[1]. Multiple isoforms exist, including membrane-associated (p63RhoGEF 580) and cytoplasmic (GEFT, p63RhoGEF 619) forms, which display differential subcellular localization and activation kinetics[2]. ARHGEF25 is implicated in cancer progression, notably in cholangiocarcinoma, and is relevant in cardiovascular physiology and pathophysiology such as hypertension[5]. Therapeutic targeting remains under investigation, with possible mechanisms centering on inhibition of pathogenic RhoA activation.

Other names

GEFTp63RhoGEFGuanine nucleotide exchange factor GEFTRac/Cdc42/Rho exchange factor GEFTRhoA/Rac/Cdc42 guanine nucleotide exchange factor GEFTRAC/CDC42 exchange factor, GEFTRhoA/RAC/CDC42 exchange factorrac/Cdc42/Rho exchange factor GEFT

Drugs targeting ARHGEF25 would likely act as inhibitors of its GEF activity for RhoA, thereby modulating actin cytoskeleton dynamics and reducing pathological contractility or proliferation[2].