Rho guanine nucleotide exchange factor 26 (ARHGEF26)

Rho guanine nucleotide exchange factor 26 (ARHGEF26) is an SH3 domain-containing GEF that activates Rho family GTPases, predominantly RhoG, by stimulating GDP-GTP exchange[1][2]. It plays a critical role in endothelial cell angiogenesis and atherosclerosis, interacting with vascular endothelial growth factor receptor 2 (VEGFR2) to facilitate signal transduction through macropinocytosis[1]. ARHGEF26 also promotes transendothelial migration of leukocytes, contributing to immune responses and plaque formation in cardiovascular disease[1]. The protein regulates inflammatory cytokine production, such as IL-8, via both GEF-dependent and GEF-independent mechanisms, and is manipulated by pathogens like Salmonella to enhance host cell invasion and inflammation[2]. ARHGEF26 is implicated in cancer, regulating cell migration and invasion, and small-molecule inhibitors against related RhoGEFs are considered promising therapeutic strategies[3]. Genetic variants in ARHGEF26 modulate its function and can impact disease risk, notably in coronary artery disease[1].

Other names

ARHGEF26SGEFSH3 domain-containing guanine nucleotide exchange factorSrc homology 3 domain-containing guanine nucleotide exchange factorCSGEFHMFN1864DKFZP434D146testicular tissue protein Li 171Rho guanine nucleotide exchange factor 26

Drugs may block its guanine nucleotide exchange activity, reducing downstream Rho GTPase activation, or disrupt ARHGEF26 signaling to impair angiogenic and inflammatory responses.