P2Y2 purinergic and M3 muscarinic acetylcholine receptors activate different phospholipase C-beta isoforms that are uniquely susceptible to protein kinase C-dependent phosphorylation and inactivation. J Biol Chem 2000 Dec 15;275(50):39767-72
Date
09/21/2000Pubmed ID
10995776DOI
10.1074/jbc.M007775200Scopus ID
2-s2.0-0034670378 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
Activation of phospholipase C-beta (PLC-beta) by G protein-coupled receptors typically results in rapid but transient second messenger generation. Although PLC-beta deactivation may contribute to the transient nature of this response, the mechanisms governing PLC-beta deactivation are poorly characterized. We investigated the involvement of protein kinase C (PKC) in the termination of PLC-beta activation induced by endogenous P2Y(2) purinergic receptors and transfected M(3) muscarinic acetylcholine receptors (mAChR) in Chinese hamster ovary cells. Activation of P2Y(2) receptors causes Galpha(q/11) to associate with PLC-beta3, whereas M(3) mAChR activation causes Galpha(q/11) to associate with both PLC-beta1 and PLC-beta3 in these cells. Phosphorylation of PLC-beta3, but not PLC-beta1, is induced by activating either P2Y(2) receptors or M(3) mAChR. We demonstrate that PKC rather than protein kinase A mediates the G protein-coupled receptor-induced phosphorylation of PLC-beta3. The PKC-mediated phosphorylation of PLC-beta3 diminishes the interaction of Galpha(q/11) with PLC-beta3, thereby contributing to the termination PLC-beta3 activity. These findings indicate that the distinct temporal profiles of PLC activation by P2Y(2) receptors and mAChR may arise from the differential activation of PLC-beta1 and PLC-beta3 by the receptors, coupled with a selective PKC-mediated negative feedback mechanism that targets PLC-beta3 but not PLC-beta1.
Author List
Strassheim D, Williams CLAuthor
Carol L. Williams PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Western
CHO Cells
Calcium
Cricetinae
Cyclic AMP-Dependent Protein Kinases
Dose-Response Relationship, Drug
Enzyme Activation
Humans
Isoenzymes
Models, Biological
Phospholipase C beta
Phosphorylation
Precipitin Tests
Protein Isoforms
Protein Kinase C
Receptor, Muscarinic M3
Receptors, Muscarinic
Receptors, Purinergic P2
Receptors, Purinergic P2Y2
Time Factors
Transfection
Type C Phospholipases