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

J. Biol. Chem., Vol. 280, Issue 13, 13084-13096, April 1, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/13/13084    most recent M410461200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Elion, E. A. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Elion, E. A. Social Bookmarking                      What's this?

Cdc24 Regulates Nuclear Shuttling and Recruitment of the Ste5 Scaffold to a Heterotrimeric G Protein in Saccharomyces cerevisiae^*

Yunmei Wang, Weidong Chen, David M. Simpson, and Elaine A. Elion

From the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115

The Saccharomyces cerevisiae guanine nucleotide exchange factor Cdc24 regulates polarized growth by binding to Cdc42, a Rho-type GTPase that has many effectors, including Ste20 kinase, which activates multiple MAPK cascades. Here, we show that Cdc24 promotes MAPK signaling during mating through interactions with Ste5, a scaffold that must shuttle through the nucleus and bind to the subunit (Ste4) of a G protein for Ste20 to activate the tethered MAPK cascade. Ste5 was basally recruited to growth sites of G₁ phase cells independently of Ste4. Loss of Cdc24 inhibited nuclear import and blocked basal and pheromone-induced recruitment of Ste5. Ste5 was not basally recruited and the MAPK Fus3 was not basally activated in the presence of a Cdc24 mutant (G168D) that still activates Cdc42, suggesting that Cdc24 regulates Ste5 and the associated MAPK cascade through a function that is not dependent on its guanine nucleotide exchange factor activity. Consistent with this, Cdc24 bound Ste5 and coprecipitated with Ste4 independently of Far1 and Ste5. Loss of Cdc24 decreased Ste5-Ste4 complex formation, and loss of Ste4 stimulated Cdc24-Ste5 complex formation. Collectively, these findings suggest that Cdc24 mediates site-specific localization of Ste5 to a heterotrimeric G protein and may therefore ensure localized activation of the associated MAPK cascade.

Received for publication, September 10, 2004 , and in revised form, January 14, 2005.

^* This work was supported by National Institutes of Health Grant GM69462 (to E. A. E.). 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.

Present address: Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.

To whom correspondence should be addressed: Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave., Boston, MA 02115. Tel.: 617-432-3815; Fax: 617-738-0516; E-mail: elaine_elion{at}hms.harvard.edu.

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

This article has been cited by other articles:

				C. Mionnet, S. Bogliolo, and R. A. Arkowitz Oligomerization Regulates the Localization of Cdc24, the Cdc42 Activator in Saccharomyces cerevisiae J. Biol. Chem., June 20, 2008; 283(25): 17515 - 17530. [Abstract] [Full Text] [PDF]

				L. Yu, M. Qi, M. A. Sheff, and E. A. Elion Counteractive Control of Polarized Morphogenesis during Mating by Mitogen-activated Protein Kinase Fus3 and G1 Cyclin-dependent Kinase Mol. Biol. Cell, April 1, 2008; 19(4): 1739 - 1752. [Abstract] [Full Text] [PDF]

				L. S. Garrenton, S. L. Young, and J. Thorner Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain Genes & Dev., July 15, 2006; 20(14): 1946 - 1958. [Abstract] [Full Text] [PDF]