Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator

Cell. 1992 Aug 7;70(3):411-8. doi: 10.1016/0092-8674(92)90165-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Catechols / pharmacology
  • Enzyme Activation
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • Hydrolysis
  • Kinetics
  • Proteins / metabolism*
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Muscarinic / metabolism
  • Turkeys
  • Type C Phospholipases / metabolism*

Substances

  • Catechols
  • GTPase-Activating Proteins
  • Proteins
  • Receptors, Adrenergic, beta
  • Receptors, Muscarinic
  • Guanosine Diphosphate
  • Atropine
  • Guanosine Triphosphate
  • Type C Phospholipases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • catechol