Coupling of the PTH/PThrP receptor to multiple G-proteins

William F. Schwindinger, Janine Fredericks, Lakrisha Watkins, Helen Robinson, Joan M. Bathon, Mark Pines, Larry J. Suva, Michael A. Levine

Research output: Contribution to journalArticlepeer-review

Abstract

Parathyroid hormone (PTH) elicits many of its physiological effects by activating distinct G-protein-coupled signaling cascades that lead to synthesis of cyclic AMP and hydrolysis of phosphatidylinositol 4,5- bisphosphate. Using the nonhydrolyzable photoreactive GTP analog [α- 32p]GTP-γ-azidoanilide (GTP-AA) and peptide antisera raised against G- protein α-sub-units, we studied coupling of the PTH receptor to G-proteins in rat osteoblast-like cells (ROS 17/2.8), and in human embryonal kidney cells expressing the cloned human PTH/parathyroid hormone-related peptide (PTHrP) receptor at 40,000 receptors/cell (C20) or 400,000 receptors/cell (C21). Incubation of C21 membranes (but not C20 membranes) with [Nle 8,18, Tyr 34]-bovine PTH(1-34) amide (bPTH[1-34]) led to concentration-dependent incorporation of GTP-AA into the two isoforms of Gα(s), into Gα(q/11), and to a much lesser extent into G(α(i(1)). In ROS 17/2.8 cells, bPTH(1-34) increased the incorporation of GTP-AA into Gα(s), but not into Gα(q/11) or Gα(i). The ability of bPTH(1-34) to increase labeling of Gα(s) and Gα(q/11) was correlated with the receptor-dependent sensitivity of the adenylyl cyclase and phospholipase C signaling pathways to the hormone.

Original languageEnglish (US)
Pages (from-to)201-209
Number of pages9
JournalEndocrine
Volume8
Issue number2
DOIs
StatePublished - 1998

Keywords

  • G-protein
  • In vitro
  • Parathyroid hormone
  • Parathyroid hormone-related peptide
  • Signal transduction

ASJC Scopus subject areas

  • Endocrinology

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