G alpha12/G alpha13 subunits of heterotrimeric G proteins mediate parathyroid hormone activation of phospholipase D in UMR-106 osteoblastic cells

Endocrinology. 2005 May;146(5):2171-5. doi: 10.1210/en.2004-1283. Epub 2005 Feb 10.


PTH, a major regulator of bone remodeling and a therapeutically effective bone anabolic agent, stimulates several signaling pathways in osteoblastic cells. Our recent studies have revealed that PTH activates phospholipase D (PLD) -mediated phospholipid hydrolysis through a RhoA-dependent mechanism in osteoblastic cells, raising the question of the upstream link to the PTH receptor. In the current study, we investigated the role of heterotrimeric G proteins in mediating PTH-stimulated PLD activity in UMR-106 osteoblastic cells. Transfection with antagonist minigenes coding for small peptide antagonists to G alpha 12 and G alpha13 subunits of heterotrimeric G proteins prevented PTH-stimulated activation of PLD, whereas an antagonist minigene to G alphas failed to produce this effect. Effects of pharmacological inhibitors (protein kinase inhibitor, Clostridium botulinum exoenzyme C3) were consistent with a role of Rho small G proteins, but not of cAMP, in the effect of PTH on PLD. Expression of constitutively active G alpha12 and G alpha13 activated PLD, an effect that was inhibited by dominant-negative RhoA. The results identify G alpha12 and G alpha13 as upstream transducers of PTH effects on PLD, mediated through RhoA in osteoblastic cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Colforsin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Enzyme Activation / drug effects*
  • Enzyme Inhibitors / pharmacology
  • GTP-Binding Protein alpha Subunits, G12-G13 / genetics
  • GTP-Binding Protein alpha Subunits, G12-G13 / physiology*
  • Gene Expression
  • Osteoblasts / enzymology*
  • Parathyroid Hormone / pharmacology*
  • Phospholipase D / metabolism*
  • Transfection
  • rhoA GTP-Binding Protein / physiology


  • Enzyme Inhibitors
  • Parathyroid Hormone
  • Colforsin
  • Cyclic AMP-Dependent Protein Kinases
  • Phospholipase D
  • GTP-Binding Protein alpha Subunits, G12-G13
  • rhoA GTP-Binding Protein