Mutational analysis of the highly conserved ERY motif of the thromboxane A2 receptor: alternative role in G protein-coupled receptor signaling

Molecular Pharmacology
Valérie CapraG E Rovati

Abstract

The presence of highly conserved amino acid stretches in G protein-coupled receptors (GPCRs) usually predicts an important role in receptor function. Considerable attention has therefore been focused on the involvement of the highly conserved Glu/Asp-Arg-Tyr (E/DRY) motif at the cytoplasmic end of transmembrane domain 3 in the regulation of GPCR conformational states and/or the mediation of G protein activation. In the present study, we investigated the role of Glu129 and Arg130 in the ERY of thromboxane A2 receptor alpha (TPalpha) in transfected human embryonic kidney 293 cells. We show that no conservative or nonconservative substitutions of Glu129 and Arg130 generated a constitutively active TPalpha mutant, but a nonconservative mutation of Arg130 (R130V) yielded a mutant receptor with significantly impaired 9,11-dideoxy-9alpha,11alpha-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U46619)-induced accumulation of inositol phosphates (IPs). This loss-of-function phenotype seems to be caused by the uncoupling of the TPalpha receptor from Gq, as demonstrated by the loss of high-affinity agonist binding, and not by receptor internalization, as shown by localization studies with the R130V-green fluorescent protein fusion protein. It...Continue Reading

References

Sep 1, 1978·The American Journal of Physiology·K M BaldwinR E Lewis
Sep 1, 1980·Analytical Biochemistry·P J Munson, D Rodbard
Oct 1, 1994·The Journal of Clinical Investigation·T HirataS Narumiya
Jan 5, 1996·Biochemical and Biophysical Research Communications·T ShibataH Miyazaki
Oct 11, 1996·The Journal of Biological Chemistry·S Acharya, S S Karnik
Feb 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·A ScheerS Cotecchia
Apr 1, 1997·Current Opinion in Cell Biology·H R Bourne
Sep 12, 1998·The Journal of Biological Chemistry·E S BursteinM R Brann
Oct 24, 1998·Trends in Pharmacological Sciences·G E Rovati
Jan 15, 1999·Pharmacology & Therapeutics·J Wess
Apr 15, 1999·The EMBO Journal·J Bockaert, J P Pin
Jan 3, 2001·Proceedings of the National Academy of Sciences of the United States of America·L S BarakM G Caron
Aug 19, 2003·European Journal of Pharmacology·Valérie CapraG Enrico Rovati
Dec 9, 2003·The Journal of Biological Chemistry·Srinivasan MadabushiOlivier Lichtarge

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Citations

Sep 30, 2006·Journal of Computer-aided Molecular Design·Francesca Fanelli, Pier G De Benedetti
Dec 10, 2008·Chemical Research in Toxicology·Alessio AmadasiPietro Cozzini
Feb 21, 2007·The Journal of Biological Chemistry·Virginie BinetLaurent Prézeau
Sep 18, 2007·Molecular Endocrinology·Krassimira AngelovaDavid Puett
Jan 8, 2011·Cellular and Molecular Life Sciences : CMLS·Francesca FanelliMarco Parenti
Dec 2, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Malvina HoxhaMassimo Bertinaria
Sep 1, 2011·General and Comparative Endocrinology·Ichiro YamamotoMinoru Tanaka
Apr 1, 2008·Pharmacology & Therapeutics·Norimichi Nakahata
Oct 30, 2007·British Journal of Pharmacology·E SelgS-E Dahlén
Jan 3, 2013·Journal of Thrombosis and Haemostasis : JTH·A D MumfordUNKNOWN UK GAPP Study Group
Mar 5, 2014·Journal of Thrombosis and Haemostasis : JTH·G E Rovati, V Capra
Dec 14, 2006·Prostaglandins & Other Lipid Mediators·Jeremiah StithamJohn Hwa
Sep 19, 2014·British Journal of Pharmacology·S P NisarUNKNOWN UK GAPP Study Group
Jul 24, 2015·Genome Biology·Diana Le DucTorsten Schöneberg
Apr 25, 2008·General and Comparative Endocrinology·Ichiro YamamotoMinoru Tanaka
Sep 27, 2013·PloS One·Christopher D Nelson, Morgan Sheng
Nov 9, 2011·Journal of Cardiovascular Pharmacology and Therapeutics·Harold J TingFadi T Khasawneh
Aug 9, 2018·Platelets·Stuart James Mundell, Andrew Mumford
Mar 23, 2006·Archives of Insect Biochemistry and Physiology·Mei-Er Chen, Patricia V Pietrantonio
Apr 28, 2005·Molecular Pharmacology·Colleen A Flanagan
Dec 29, 2006·Molecular Pharmacology·G Enrico RovatiRichard R Neubig
Feb 2, 2008·The Biochemical Journal·Doreen ThorTorsten Schöneberg
Aug 28, 2012·Eukaryotic Cell·Austin U GehretMark E Dumont
Nov 23, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hitoo TokunagaMorikazu Onji
Sep 1, 2009·Molecular Pharmaceutics·Mario BrufaniAdriana Maggi
Mar 14, 2008·Journal of the American Chemical Society·Francesco RaimondiFrancesca Fanelli

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