GTPase-Activating Proteins (GAPs) for Heterotrimeric G Proteins

G protein signaling is controlled by the binding and hydrolysis of GTP on Gα subunits. The rate of receptor-stimulated GTP binding primarily controls the rate of initial activation, and the rate of hydrolysis determines the rate of signal termination. Together, the balance of these rates determines the steady-state signal amplitude. Isolated G proteins hydrolyze bound GTP slowly (t 1/2 ~ 10–20 s for G i , G t , G o , G s 1–3 ; ~1 min for G q 4 ; ~7 min for G z 5 , 6 ), and these rates are often far slower than the termination rates of G protein-mediated signals. GTPase-activating proteins, GAPs, accelerate hydrolysis by G proteins over 200-fold, and thus GAPs confer the speed needed for reliable cellular signaling.