The role of sequestration in G protein-coupled receptor resensitization. Regulation of beta2-adrenergic receptor dephosphorylation by vesicular acidification.

The Journal of Biological Chemistry
K M KruegerR J Lefkowitz

Abstract

G protein-coupled receptor kinases phosphorylate the agonist occupied conformation of G protein-coupled receptors in the plasma membrane, leading to their desensitization. Receptor resensitization requires receptor dephosphorylation, a process which is mediated by a plasma and vesicular membrane-associated form of PP-2A. We present evidence that, like receptor phosphorylation, receptor dephosphorylation is tightly regulated, requiring a specific receptor conformation induced by vesicular acidification. In vitro, spontaneous dephosphorylation of phosphorylated receptors is observed only at acidic pH. Furthermore, in intact cells upon agonist stimulation, phosphorylated receptors traffic from the plasma membrane to vesicles where they become physically associated with the phosphatase and dephosphorylated. Treatment of cells with NH4Cl, which disrupts the acidic pH found in endosomal vesicles, blocks association of the receptors with the phosphatase and blocks receptor dephosphorylation. These findings suggest that a conformational change in the receptor induced by acidification of the endosomal vesicles is the key determinant regulating receptor dephosphorylation and resensitization.

References

Jan 1, 1991·Annual Review of Biochemistry·H G DohlmanR J Lefkowitz
Oct 1, 1991·Trends in Biochemical Sciences·K Palczewski, J L Benovic
Jan 1, 1989·Annual Review of Cell Biology·J Gruenberg, K E Howell
Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·D R SibleyR J Lefkowitz
Jan 1, 1984·Methods in Enzymology·S Shenolikar, T S Ingebritsen
Apr 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·A Dautry-VarsatH F Lodish
Dec 8, 1995·The Journal of Biological Chemistry·G KrapivinskyD E Clapham
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·J A PitcherR J Lefkowitz
Feb 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R T PremontR J Lefkowitz

❮ Previous
Next ❯

Citations

May 27, 1999·Electrophoresis·J Godovac-ZimmermannF Brianza
Nov 22, 2001·Biochemical and Biophysical Research Communications·T AwajiS Miyazaki
Aug 31, 2000·Cell Biology International·J T DjordjevicK K Stanley
Oct 12, 2005·Pflügers Archiv : European journal of physiology·Hjalmar BrismarUlla Holtbäck
Apr 18, 2013·Invertebrate Neuroscience : in·Arkady S PivovarovNatalya A Vasil'yeva
Oct 6, 2010·Journal of Fluorescence·Felix H C Wong, Cécile Fradin
Nov 6, 2010·Archives of Pharmacal Research·Dong Im ChoKyeong-Man Kim
Nov 11, 2003·Life Sciences·Jennifer L Seachrist, Stephen S G Ferguson
Nov 11, 2003·Life Sciences·Hiroshi UedaKiyonobu Mizuno
Nov 9, 2000·European Journal of Pharmacology·N ParameswaranW S Spielman
May 3, 2003·Pharmacology & Therapeutics·Chris J van Koppen, Björn Kaiser
Dec 22, 1999·Pharmacology & Therapeutics·C Saunders, L E Limbird
Apr 29, 2000·Trends in Pharmacological Sciences·L Kallal, J L Benovic
Sep 1, 2000·Regulatory Peptides·L HunyadyZ Gáborik
Feb 8, 2003·Brain Research. Molecular Brain Research·James D FosterRoxanne A Vaughan
Feb 28, 2004·Trends in Cardiovascular Medicine·F MayorA Ruiz-Gómez
Mar 30, 2001·The Journal of Biological Chemistry·G H FanA Richmond
Jun 13, 2009·The Journal of Biological Chemistry·Van Anthony M VillarPedro A Jose
Sep 1, 2009·The Journal of Biological Chemistry·Lucimar T FerreiraStephen S G Ferguson
Oct 21, 2010·The Journal of Biological Chemistry·Cornelia WaltherAnnette G Beck-Sickinger
Feb 24, 2011·The Journal of Biological Chemistry·Madhumita Ghosh, Agnes Schonbrunn
Jun 29, 2011·The Journal of Biological Chemistry·Aneta DobierzewskaMariana N Nikolova-Karakashian
Oct 27, 2006·The Journal of Biological Chemistry·Violaine SimonStephen M Lanier
Mar 14, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Deepak A DeshpandeJulia K L Walker
Nov 5, 1997·European Journal of Biochemistry·K Palczewski
Apr 30, 2010·Pharmacological Reviews·Louis M Luttrell, Diane Gesty-Palmer
Jul 29, 2011·American Journal of Physiology. Cell Physiology·Jane E MurphyMartin Steinhoff
Dec 9, 2010·American Journal of Physiology. Endocrinology and Metabolism·Konstantinos DrosatosIra J Goldberg
Jun 23, 2009·Molecular Endocrinology·Brian W Jones, Patricia M Hinkle
Jul 28, 2011·Microbes and Environments·Alena ŠevcůMiroslav Černík
Jan 26, 2010·PLoS Computational Biology·Sharat J VayttadenRichard B Clark

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.