A built-in arginine finger triggers the self-stimulatory GTPase-activatingactivity of Rho family GTPases

Signal transduction through the Rho family GTPases requires regulated cycli ng of the GTPases between the active GTP-bound state and the inactive GDP-b ound state. Rho family members containing an arginine residue at position 1 86 in the C-terminal polybasic region were found to possess a self-stimulat ory GTPase-activating protein (GAP) activity through hemophilic interaction , resulting in significantly enhanced intrinsic GTPase activities. This arg inine residue functions effectively as an "arginine finger" in the GTPase a ctivating reaction to confer the catalytic GAP activity but is not essentia l for the hemophilic binding interactions of Rho family proteins. The argin ine 186-mediated negative regulation seems to be absent from Cdc42, a Rho f amily member important for cell-division cycle regulation, of lower eukaryo tes, yet appears to be a part of the turn-off machinery of Cdc42 from highe r eukaryotes, Introduction of the arginine 186 mutation into S, cerevisiae CDC42 led to phenotypes consistent with down-regulated CDC42 function. Thus , specific Rho family GTPases may utilize a built-in arginine finger, in ad dition to RhoGAPs, for negative regulation.