GTPase activity associates with the inhibitory GTP-binding regulatory component of adenylate cyclase purified from rat brain.

The inhibitory regulatory component of adenylate cyclase (Ni) was highly purified from rat brain synaptic membranes. A low Km GTPase activity was always associated with Ni through the purification, and the recovery of GTPase activity correlated well with that of Ni. Purified Ni was hardly ADP-ribosylated by islet-activating protein (IAP). A heat-labile factor in the fraction of the stimulative regulatory component (Ns) restored ADP-ribosylation and also activated the GTPase about 2-fold. NaF which was reported to interact with Ni markedly reduced GTPase activity. The purified Ni fraction inhibited adenylate cyclase only in the presence of a heat-stable factor found in the partially purified regulatory component. GTPase and inhibitory activities were weak in myelin which contained only a small amount of Ni. These findings support the view that GTPase activity is an intrinsic activity of Ni and some factors are necessary for the function of Ni.