Rho guanine nucleotide exchange factor 17 (ARHGEF17)

Rho guanine nucleotide exchange factor 17 (ARHGEF17) is a member of the Dbl family of guanine nucleotide exchange factors that activate Rho family GTPases, notably RhoA[1][2][3][4]. Through its Dbl homology (DH) domain, ARHGEF17 catalyzes exchange of GDP for GTP on RhoA, promoting downstream signaling events crucial for actin cytoskeleton organization and cell junction integrity—especially in vascular endothelial cells[1][3]. It contains DH, pleckstrin homology (PH), and β-propeller domains involved in protein-protein interactions and lipid binding[1]. ARHGEF17 is necessary for maintaining endothelial junctions, and its depletion or mutation is associated with defective vessel integrity and increased risk of intracranial aneurysm and hemorrhage in model organisms and humans[1]. It is also expressed during tumor-induced angiogenesis and may contribute to vascular remodeling in cancer[1]. Activation of ARHGEF17 is regulated by phosphorylation via cyclic GMP-dependent kinase Iα, altering its ability to activate RhoA and its downstream effectors[2]. Disease-associated mutations and genetic risk variants have been identified, implicating ARHGEF17 in both cerebrovascular disorders and potentially in cancer biology[1][2][3][4]. No direct therapeutic drugs targeting ARHGEF17 are reported, but it represents a candidate target for modulating vascular integrity and related pathologies.

Other names

KIAA0337TEM4p164-RhoGEFRho-specific guanine-nucleotide exchange factor 164 kDaTumor endothelial marker 4RHOGEF17P164RHOGEFARHGH8030463K16AI428794AW558066mKIAA0337

Activation of RhoA GTPases and downstream RhoA-ROCK pathway via guanine nucleotide exchange; phosphorylation/activation by cGMP-dependent kinase Iα