Antagonist minigenes identify genes regulated by parathyroid hormone through G protein-selective and G protein co-regulated mechanisms in osteoblastic cells

J. Wang*, A. Gilchrist, P. H. Stern

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Parathyroid hormone (PTH) is the major hormone regulating bone remodeling. Binding of PTH to the PTH1 receptor (PTH1R), a heterotrimeric G protein coupled receptor (GPCR), can potentially trigger multiple signal transduction pathways mediated through several different G proteins. In this study, we employed G protein antagonist minigenes inhibiting Gαs, Gαq or Gα12 to selectively dissect out which of these G proteins were responsible for effects of PTH(1-34) in targeted signaling and osteogenesis arrays consisting of 159 genes. Among the 32 genes significantly regulated by 24h PTH treatment in UMR-106 osteoblastic cells, 9 genes were exclusively regulated through Gs, 6 genes were solely mediated through Gq, and 3 genes were only controlled through G12. Such findings support the concept that there is some absolute specificity in downstream responses initiated at the G protein level following binding of PTH to the PTH1R. On the other hand, 6 PTH-regulated genes were regulated by both Gs and Gq, 3 genes were regulated by both Gs and G12, and 3 genes were controlled by Gs, Gq and G12. These findings indicate potential overlapping or sequential interactions among different G protein-mediated pathways. In addition, two PTH-regulated genes were not regulated through any of the G proteins examined, suggesting that additional signaling mechanisms may be involved. Selectivity was largely maintained over a 2-48-hour time period. The minigene effects were mimicked by downstream inhibitors. The dissection of the differential effects of multiple G protein pathways on gene regulation provides a more complete understanding of PTH signaling in osteoblastic cells.

Original languageEnglish (US)
Pages (from-to)380-388
Number of pages9
JournalCellular Signalling
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 1 2011

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Keywords

  • G protein
  • Gene array
  • Minigene
  • Osteoblast
  • Parathyroid hormone

ASJC Scopus subject areas

  • Cell Biology

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