The N-terminal region of the third intracellular loop of the parathyroid hormone (PTH)/PTH-related peptide receptor is critical for coupling to cAMP and inositol phosphate/Ca2+ signal transduction pathways.

The Journal of Biological Chemistry
Z HuangD Shoback

Abstract

Structural determinants within the parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor that mediate G-protein activation of adenylate cyclase and phospholipase C are unknown. We investigated the role of the N-terminal region of the third intracellular loop of the opossum PTH/PTHrP receptor in coupling to two signal transduction pathways. We mutated residues in this region by tandem-alanine scanning and expressed these mutant receptors in COS-7 cells and/or Xenopus oocytes. All mutant receptors retained high affinity PTH binding in COS-7 cells, indistinguishable from wild-type receptors. Receptors with tandem-alanine substitutions in two N-terminal segments (377RVL379 and 381TKLR384) demonstrated impaired adenylate cyclase and phospholipase C activation. Receptor mutants with single-alanine substitutions scanning these two segments showed three different signaling defects in COS-7 cells. 1) Two mutant receptors (V378A and L379A) had reduced inositol phosphate (IP), but normal cAMP responses to PTH. 2) Mutant receptor T381A showed reduced cAMP, but wild-type IP responses to PTH. 3) Mutant receptor K382A demonstrated both markedly reduced cAMP and IP production due to PTH. In oocytes, mutants T381A and K382A showed decr...Continue Reading

References

Jan 1, 1992·Annual Review of Pharmacology and Toxicology·J OstrowskiR J Lefkowitz
Jan 1, 1992·Methods in Enzymology·Y Oron, N Dascal
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M M White, T Reisine
Nov 11, 1990·The American Journal of Physiology·L J GreenfieldJ Linden
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·R E StraubM C Gershengorn
Feb 1, 1994·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·T H ChenD M Shoback
Dec 1, 1993·Endocrine Reviews·D W DempsterR Lindsay
Dec 15, 1995·The Journal of Biological Chemistry·L Stehno-BittelD E Clapham
Jan 1, 1996·Physiological Reviews·W M PhilbrickA F Stewart

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Citations

Apr 23, 2002·Journal of Cellular Biochemistry·Kannan ThirunavukkarasuJude E Onyia
Jan 15, 1999·Pharmacology & Therapeutics·J Wess
Jan 12, 2000·Molecular and Cellular Endocrinology·W ChangD Shoback
Sep 9, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·A Sidhu, H B Niznik
Jun 9, 2001·Trends in Endocrinology and Metabolism : TEM·T J Gardella, H Jüppner
Oct 21, 2009·The Journal of Pharmacology and Experimental Therapeutics·Jean-Philippe FortinAlan S Kopin
Jan 27, 2012·American Journal of Physiology. Cell Physiology·Gene L GarciaLaurence J Miller
Jun 26, 2008·American Journal of Physiology. Endocrinology and Metabolism·Susanne U Miedlich, Abdul B Abou-Samra
May 3, 2008·BMC Evolutionary Biology·N KameshNarayanan Manoj
Apr 29, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·W ChangD Shoback
Nov 26, 2015·Frontiers in Pharmacology·Kelly J CulhaneElsa C Y Yan
Jan 18, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Beena E ThomasMichael Rosenblatt
May 26, 2007·Protein Science : a Publication of the Protein Society·Tim J KamerzellC Russell Middaugh
Jan 21, 2012·Biochemical Society Transactions·Colin W Taylor, Stephen C Tovey
Jun 20, 2017·The FEBS Journal·Sai Krishna AndhirkaGopala Krishna Aradhyam
Aug 16, 2018·Physiological Reviews·Jan M Deussing, Alon Chen
Mar 8, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yuansheng Gao, J Usha Raj
Jun 26, 1999·The Journal of Biological Chemistry·A M CypessT P Sakmar
Dec 1, 2001·The Journal of Biological Chemistry·Jean-Pierre VilardagaRobert A Nissenson
Jul 11, 2002·The Journal of Biological Chemistry·Alessandro BiselloSerge L Ferrari
Jun 3, 2018·Hormones : International Journal of Endocrinology and Metabolism·Vlasios KarageorgosGeorge Liapakis
Nov 24, 1999·The American Journal of Physiology·M MannstadtT J Gardella

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