Two homologous phosphorylation domains differentially contribute to desensitization and internalization of the m2 muscarinic acetylcholine receptor.

The Journal of Biological Chemistry
R Pals-Rylaarsdam, M M Hosey

Abstract

Short term exposure of m2 muscarinic acetylcholine receptors (m2 mAChRs) to agonist causes a rapid phosphorylation of the activated receptors, followed by a profound loss in the ability of the m2 mAChR to activate its signaling pathways. We have used site-directed mutagenesis to identify two clusters of Ser/Thr residues in the third intracellular loop of the m2 mAChR that can serve as redundant targets for agonist-dependent phosphorylation. Mutation of both clusters of Ser/Thr residues to alanines abolished agonist-dependent phosphorylation, while wild-type levels of m2 mAChR phosphorylation were observed in mutant receptors with only one or the other cluster mutated. However, the functional effects of phosphorylation of these two "redundant" clusters were not equivalent. No receptor desensitization was observed in an m2 mAChR with residues Thr307-Ser311 mutated to alanine residues. In contrast, mutation of the other Ser/Thr cluster, residues Ser286-Ser290, to alanines produced a receptor that continued to desensitize. Internalization of the m2 mAChR was promoted by phosphorylation of either cluster, suggesting that distinct mechanisms with unique structural requirements act downstream of m2 mAChR phosphorylation to mediate rec...Continue Reading

References

Apr 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·R L WeinshankP R Hartig
Jan 1, 1991·Methods in Enzymology·R A Johnson, Y Salomon
Jan 1, 1995·Steroids·H NawataK Ohe
Aug 13, 1993·Cell·R J Lefkowitz
May 11, 1993·Biochemistry·J H McDowellP A Hargrave
Jun 1, 1993·Biochemistry·H OhguroR S Johnson

❮ Previous
Next ❯

Citations

Aug 27, 2013·Current Genetics·José Miguel MuletLynne Yenush
Aug 17, 1999·European Journal of Pharmacology·M S ShockleyJ Lameh
May 3, 2003·Pharmacology & Therapeutics·Chris J van Koppen, Björn Kaiser
Sep 24, 1998·Trends in Pharmacological Sciences· Haddad el-B, J Rousell
Jul 10, 2003·Molecular and Cellular Endocrinology·Hanumanthappa KrishnamurthyMario Ascoli
Nov 16, 2001·Trends in Cardiovascular Medicine·R D Lasley, E J Smart
Jun 20, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yinglong MiaoJ Andrew McCammon
Oct 10, 2009·The Journal of Biological Chemistry·Tiffany K Ricks, JoAnn Trejo
Jan 26, 2012·The Journal of Biological Chemistry·Luis E GimenezVsevolod V Gurevich
Sep 19, 2008·Journal of Toxicology and Environmental Health. Part a·Elmar M Udarbe ZamoraCarey N Pope
Nov 5, 1997·European Journal of Biochemistry·K Palczewski
Apr 1, 1999·Annual Review of Physiology·M BünemannM M Hosey
Jan 17, 2007·Journal of Molecular Signaling·Kymry T JonesDarrell A Jackson
Nov 12, 2005·Critical Reviews in Clinical Laboratory Sciences·Miles D ThompsonDavid E C Cole
May 20, 2015·Membranes·Wymke Ockenga, Ritva Tikkanen
May 5, 1999·The Journal of Physiology·M Bünemann, M M Hosey
Jun 6, 2012·Cellular Signalling·Vsevolod V Gurevich, Eugenia V Gurevich
Mar 31, 2009·International Journal for Parasitology·Michael J KimberPaula Ribeiro
Jan 15, 2008·British Journal of Pharmacology·A B Tobin
Jan 20, 2011·Journal of Neurochemistry·Rebecca StadelDebra A Kendall
Jun 15, 2005·Neuron·Heather L AglerDavid T Yue
Oct 15, 1998·Experimental Cell Research·R PfeifferF Fahrenholz
Nov 9, 2002·The Journal of Biological Chemistry·T Alexander KeyEric R Prossnitz
Sep 20, 1997·The Journal of Biological Chemistry·R Pals-RylaarsdamM M Hosey
Apr 13, 2007·American Journal of Physiology. Renal Physiology·Martin H de BorstHarry van Goor
Mar 14, 2008·The Journal of Pharmacology and Experimental Therapeutics·Yuichi HashimotoTatsuya Haga
Jan 22, 2001·The Journal of Biological Chemistry·Z ShuiM R Boyett

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.