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.
| Original language | English |
|---|---|
| Pages (from-to) | 411-418 |
| Number of pages | 8 |
| Journal | Cell |
| Volume | 70 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 7 Aug 1992 |
| Externally published | Yes |
Keywords
- 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