Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator.
Purified M1 muscarinic cholinergic receptor and Gq/11 were coreconstituted in lipid vesicles. Addition of purified phospholipase C-beta 1 (PLC-beta 1) further stimulated the receptor-promoted steady-state GTPase activity of Gq/11 up to 20-fold. Stimulation depended upon receptor-mediated GTP-GDP exchange. Addition of PLC-beta 1 caused a rapid burst of hydrolysis of Gq/11-bound GTP that was at least 50-fold faster than in its absence. Thus, PLC-beta 1 stimulates hydrolysis of Gq/11-bound GTP and acts as a GTPase-activating protein (GAP) for its physiologic regulator, Gq/11. GTPase-stimulating activity was specific both for PLC-beta 1 and Gq/11. Such GAP activity by an effector coupled to a trimeric G protein can reconcile slow GTP hydrolysis by pure G proteins in vitro with fast physiologic deactivation of G protein-mediated signaling.
Berstein
G
G
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235-9041.
Blank
J L
JL
Jhon
D Y
DY
Exton
J H
JH
Rhee
S G
SG
Ross
E M
EM
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002396:Catechols / Q000494:pharmacology; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D011506:Proteins / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D014422:Turkeys; D010738:Type C Phospholipases / Q000378:metabolism*
D002396:Catechols; D020690:GTPase-Activating Proteins; D011506:Proteins; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D006153:Guanosine Diphosphate; D001285:Atropine; D006160:Guanosine Triphosphate; D010738:Type C Phospholipases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C034221:catechol