MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on January 17, 2006; DOI: 10.1124/mol.105.019703

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.105.019703v1
69/4/1433    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, L.
Right arrow Articles by Manning, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, L.
Right arrow Articles by Manning, D. R.


Received for publication October 7, 2005.
Revised December 23, 2005.
Accepted for publication January 13, 2006.

The G12 Family of G Proteins as a Reporter of Thromboxane A2 Receptor Activity

Li Zhang 1, Cherisse DiLizio 1, David Kim 1, Emer Smyth 1, David R. Manning 1*

1 University of Pennsylvania

* Address correspondence to: E-mail: manning{at}pharm.med.upenn.edu

Abstract

Despite advances in the understanding of pathways regulated by the G12 family of heterotrimeric G proteins, much regarding the engagement of this family by receptors remains unclear. We explore here, using the thromboxane A2 receptor TP{alpha}, the ability of G12 and G13 to report differences in the potency and efficacy of receptor ligands. We were interested especially in the potential of the isoprostane 8-iso-prostaglandin F2{alpha} (8-iso-PGF2{alpha}), among other ligands examined, to activate G12 and G13 through TP{alpha} explicitly. We were also interested in the functionality of TP{alpha}·G{alpha} fusion proteins germane to G12 and G13. Using fusion proteins in Sf9 cells and independently expressed proteins in HEK293 cells, and using [35S]GTP{gamma}S-binding to evaluate G{alpha} activation directly, we found for G{alpha}13 that no ligand tested, including 8-iso-PGF2{alpha} and a purported antagonist (pinane thromboxane A2), was silent. The activity of agonists was especially pronounced when evaluated for TP{alpha}·G{alpha}13 and in the context of receptor reserve. Agonist activity for 8-iso-PGF2{alpha} was diminished, and that for pinane thromboxane A2 nonexistent, when G{alpha}12 was the reporter. These data establish that G12 and G13 can report differentially potency and efficacy, and they underscore the relevance of receptor and G protein context.


Key words: Prostanoid, G12,13;other G's, G protein regulation


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. Wada, C. J. DeLong, Y. H. Hong, C. J. Rieke, I. Song, R. S. Sidhu, C. Yuan, M. Warnock, A. H. Schmaier, C. Yokoyama, et al.
Enzymes and Receptors of Prostaglandin Pathways with Arachidonic Acid-derived Versus Eicosapentaenoic Acid-derived Substrates and Products
J. Biol. Chem., August 3, 2007; 282(31): 22254 - 22266.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. D. Hildebrandt
Bring Your Own G Protein
Mol. Pharmacol., April 1, 2006; 69(4): 1079 - 1082.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2006 by the American Society for Pharmacology and Experimental Therapeutics