HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 34, 35287-35297, August 20, 2004

This Article Full Text Full Text (PDF) An addition or correction has been published All Versions of this Article: 279/34/35287    most recent M404896200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, Y.-L. Articles by Dohlman, H. G. Search for Related Content PubMed PubMed Citation Articles by Wu, Y.-L. Articles by Dohlman, H. G. Social Bookmarking                      What's this?

Dominant-negative Inhibition of Pheromone Receptor Signaling by a Single Point Mutation in the G Protein Subunit^*

Yuh-Lin Wu, Shelley B. Hooks, T. Kendall Harden, and Henrik G. Dohlman¶

From the Department of Biochemistry and Biophysics and the Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599-7260

In yeast, two different constitutive mutants of the G protein subunit have been reported. Gpa1^Q323L cannot hydrolyze GTP and permanently activates the pheromone response pathway. Gpa1^N388D was also proposed to lack GTPase activity, yet it has an inhibitory effect on pheromone responsiveness. We have characterized this inhibitory mutant (designated G^ND) and found that it binds GTP, interacts with G protein subunits, and exhibits full GTPase activity in vitro. Although pheromone leads to dissociation of the receptor from wild-type G protein, the same treatment promotes stable association of the receptor with G^ND. We conclude that agonist binding to the receptor promotes the formation of a nondissociable complex with G^ND, and in this manner prevents activation of the endogenous wild-type G protein. Dominant-negative mutants may be useful in matching specific receptors and their cognate G proteins and in determining mechanisms of G protein signaling specificity.

Received for publication, May 3, 2004 , and in revised form, June 9, 2004.

^* This work was supported by National Institutes of Health Grants P01-GM65533 (to T. K. H. and H. G. D.) and F32-GM66561 (to S. B. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Dept. of Biochemistry and Biophysics, University of North Carolina, CB 7260, Chapel Hill, NC 27599-7260. Tel.: 919-843-6894; Fax: 919-966-2852; E-mail: hdohlman{at}med.unc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. S. Hoffman Except in Every Detail: Comparing and Contrasting G-Protein Signaling in Saccharomyces cerevisiae and Schizosaccharomyces pombe Eukaryot. Cell, March 1, 2005; 4(3): 495 - 503. [Full Text] [PDF]