Rho GTPase Activating Protein 15 (ARHGAP15)

RHO GTPases regulate diverse biologic processes, and their activity is regulated by RHO GTPase-activating proteins (GAPs), such as ARHGAP15. The deduced 475-amino acid protein contains an N-terminal pleckstrin homology (PH) domain and a C-terminal GAP domain, which is highly similar to the GAP domains of ARHGAP9 and ARHGAP12. In COS-7 and HeLa cells, overexpression of the full-length protein but not of the PH domain-truncated mutant resulted in an increase in actin stress fibers and cell contraction. These morphologic effects were attenuated by coexpression of a dominant-negative RAC1 mutant. HeLa cells expressing ARHGAP15 were also resistant to phorbol ester treatment, suggesting that ARHGAP15 is a regulator of RAC1.