Rho GTPase-activating protein 9 (ARHGAP9)

Rho GTPase-activating protein 9 (ARHGAP9) is an enzyme belonging to the Rho-GAP family that inactivates Rho-type GTPases, especially CDC42 and RAC1, by promoting GTP hydrolysis and thus terminating their signaling[5]. ARHGAP9 contains multiple functional domains (SH3, WW, PH, RhoGAP), allowing it to act both as a GTPase-activator and as a docking protein for MAP kinases, specifically Erk2 and p38α, suppressing their activity and influencing actin dynamics[1][3]. It plays roles in cell adhesion, cytoskeletal organization, the immune response, and cell cycle regulation. It is implicated in several diseases, notably acting as a prognostic marker and functional regulator in acute myeloid leukemia and diverse solid tumors, with expression level linked to outcome[3][5]. Experimental disruption of ARHGAP9-MAP kinase interactions represents a novel therapeutic approach[1].

Other names

ARHGAP9MGC129510CRGL1Rho-type GTPase-activating protein 9rho GTPase-activating protein 9rho-type GTPase-activating protein 9

Small molecules that disrupt ARHGAP9-MAP kinase interactions inhibit MAP kinase activation, offering selective inhibition compared to ATP-competitive inhibitors[1].