Role of protein kinase A, phospholipase C and phospholipase D in parathyroid hormone receptor regulation of protein kinase Cα and interleukin-6 in UMR-106 osteoblastic cells

Julie M. Radeff, Amareshwar T.K. Singh, Paula H. Stern*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Parathyroid hormone (PTH) stimulates both bone formation and resorption by activating diverse osteoblast signalling pathways. Upstream signalling for PTH stimulation of protein kinase C-α (PKCα) membrane translocation and subsequent expression of the pro-resorptive cytokine interleukin-6 (IL-6) was investigated in UMR-106 osteoblastic cells. PTH 1-34, PTH 3-34, PTHrP and PTH 1-31 stimulated PKCα translocation and IL-6 promoter activity. Pharmacologic intervention at the adenylyl cyclase (AC) pathway (forskolin, IBMX, PKI) failed to alter PTH 1-34- or PTH 3-34-stimulated PKCα translocation. The phosphoinositol-phospholipase C (PI-PLC) antagonist U73122 slightly decreased PTH 1-34-stimulated PKCα translocation; however, the control analogue U73343 acted similarly. Propranolol, an inhibitor of phosphatidic acid (PA) phosphohydrolase, decreased diacylglycerol (DAG) formation and attenuated PTH 1-34- and PTH 3-34-stimulated PKCα translocation and IL-6 promoter activity, suggesting a phospholipase D (PLD)-dependent mechanism. This is the first demonstration that PLD-mediated signalling leads to both PKC-α translocation and IL-6 promoter activation in osteoblastic cells.

Original languageEnglish (US)
Pages (from-to)105-114
Number of pages10
JournalCellular Signalling
Volume16
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • Interleukin-6
  • Osteoblast
  • Parathyroid hormone
  • Phospholipase D
  • Protein kinase C isozymes

ASJC Scopus subject areas

  • Cell Biology

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