Regulation of the M1 muscarinic receptor-G_g-phospholipase C-β pathway by nucleotide exchange and GTP hydrolysis

M1 muscarinic choligernic receptor, G_q and G₁₁ (G _{q 11}), and phospholipase C-β1 were highly purified from both natural sources and cells that express the appropriate cDNA's. When the proteins were co-reconstituted in into phospholipid vesicles, the receptor efficiently and selectively promoted the activation of if G _{q 11}, leading to marked stimulation of PLC activity in the presence of GTPγS. No stimulation was observed in the presence of GTP, however, which led to the finding that PLC-β1 stimulates the hydrolysis of if G _{q 11}-bound GTP at leasr 50-fold. Thus, PLC-β1 is a GTPase activating protein, a GAP, for its physiologic regulator G in q 11. We discuss the implications of PLC- β1's GAP activity on the M1 muscarinic cholinergic signaling pathway.