help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on February 10, 2005
Endocrinology, doi:10.1210/en.2004-1283
A more recent version of this article appeared on May 1, 2005
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
146/5/2171    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Singh, A. T.K.
Right arrow Articles by Stern, P. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Singh, A. T.K.
Right arrow Articles by Stern, P. H.

Submitted on September 29, 2004
Accepted on February 2, 2005

G{alpha}12/G{alpha}13 Subunits of Heterotrimeric G Proteins Mediate Parathyroid Hormone Activation of Phospholipase D in UMR-106 Osteoblastic Cells

A. T.K. Singh, A. Gilchrist, T. Voyno-Yasenetskaya, J. M. Radeff-Huang, and P. H. Stern*

Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, IL, Cue BIOtech Evanston, IL, Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL

* To whom correspondence should be addressed. E-mail: p-stern{at}northwestern.edu.

Parathyroid hormone (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 {rho} A-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{alpha}13 subunits of heterotrimeric G proteins prevented PTH-stimulated activation of PLD, whereas an antagonist minigene to G{alpha}s failed to produce this effect. Effects of pharmacological inhibitors (PKI, C. 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{alpha}12 and G{alpha}13 activated PLD, an effect that was inhibited by dominant negative {rho} A. The results identify G{alpha}12 and G{alpha}13 as upstream transducers of PTH effects on phospholipase D, mediated through RhoA in osteoblastic cells.
Key words: Parathyroid hormone • osteoblast • phospholipase D • G protein • Rho A




This article has been cited by other articles:


Home page
 Mol. Cell. Biol.Home page
S. Provot, G. Nachtrab, J. Paruch, A. P. Chen, A. Silva, and H. M. Kronenberg
A-Raf and B-Raf Are Dispensable for Normal Endochondral Bone Development, and Parathyroid Hormone-Related Peptide Suppresses Extracellular Signal-Regulated Kinase Activation in Hypertrophic Chondrocytes
Mol. Cell. Biol., January 1, 2008; 28(1): 344 - 357.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
T. Dean, A. Linglart, M. J. Mahon, M. Bastepe, H. Juppner, J. T. Potts Jr., and T. J. Gardella
Mechanisms of Ligand Binding to the Parathyroid Hormone (PTH)/PTH-Related Protein Receptor: Selectivity of a Modified PTH(1-15) Radioligand for G{alpha}S-Coupled Receptor Conformations
Mol. Endocrinol., April 1, 2006; 20(4): 931 - 943.
[Abstract] [Full Text] [PDF]

Home page
 IBMS BoneKEyHome page
H. M. Kronenberg
How PTHrP Controls Growth Plate Chondrocytes
IBMS BoneKEy, November 1, 2005; 2(11): 7 - 15.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2005 by The Endocrine Society