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

J. Biol. Chem., Vol. 279, Issue 45, 47391-47401, November 5, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/45/47391    most recent M405681200v1 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 Flotho, A. Articles by Elion, E. A. Search for Related Content PubMed PubMed Citation Articles by Flotho, A. Articles by Elion, E. A. Social Bookmarking                      What's this?

Localized Feedback Phosphorylation of Ste5p Scaffold by Associated MAPK Cascade^*

Annette Flotho, David M. Simpson, Maosong Qi, and Elaine A. Elion

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

Scaffold proteins play pivotal roles during signal transduction. In Saccharomyces cerevisiae, the Ste5p scaffold protein is required for activation of the mating MAPK cascade in response to mating pheromone and assembles a G protein-MAPK cascade complex at the plasma membrane. To serve this function, Ste5p undergoes a regulated localization event involving nuclear shuttling and recruitment to the cell cortex. Here, we show that Ste5p is also subject to two types of phosphorylation and increases in abundance as a result of MAPK activation. During vegetative growth, Ste5p is basally phosphorylated through a process regulated by the CDK Cdc28p. During mating pheromone signaling, Ste5p undergoes increased phosphorylation by the mating MAPK cascade. Multiple kinases of the mating MAPK cascade contribute to pheromone-induced phosphorylation of Ste5p, with the mating MAPKs contributing the most. Pheromone induction or overexpression of the Ste4p G subunit increases the abundance of Ste5p at a post-translational step, as long as the mating MAPKs are present. Increasing the level of MAPK activation increases the amount of Ste5p at the cell cortex. Analysis of Ste5p localization mutants reveals a strict requirement for Ste5p recruitment to the plasma membrane for the pheromone-induced phosphorylation. These results suggest that the pool of Ste5p that is recruited to the plasma membrane selectively undergoes feedback phosphorylation by the associated MAPKs, leading to an increased pool of Ste5p at the site of polarized growth. These findings provide evidence of a spatially regulated mechanism for post-activation control of a signaling scaffold that potentiates pathway activation.

Received for publication, May 21, 2004 , and in revised form, July 16, 2004.

^* This work was supported by National Institutes of Health R.O.1 Grant GM46962 (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: Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.

To whom correspondence should be addressed. 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:

				Y. Mazor and M. Kupiec Developmentally regulated MAPK pathways modulate heterochromatin in Saccharomyces cerevisiae Nucleic Acids Res., June 11, 2009; (2009) gkp512v1. [Abstract] [Full Text] [PDF]

				L. S. Garrenton, A. Braunwarth, S. Irniger, E. Hurt, M. Kunzler, and J. Thorner Nucleus-Specific and Cell Cycle-Regulated Degradation of Mitogen-Activated Protein Kinase Scaffold Protein Ste5 Contributes to the Control of Signaling Competence Mol. Cell. Biol., January 15, 2009; 29(2): 582 - 601. [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]

				R. P. Bhattacharyya, A. Remenyi, M. C. Good, C. J. Bashor, A. M. Falick, and W. A. Lim The Ste5 Scaffold Allosterically Modulates Signaling Output of the Yeast Mating Pathway Science, February 10, 2006; 311(5762): 822 - 826. [Abstract] [Full Text] [PDF]

				Y. Wang, W. Chen, D. M. Simpson, and E. A. Elion Cdc24 Regulates Nuclear Shuttling and Recruitment of the Ste5 Scaffold to a Heterotrimeric G Protein in Saccharomyces cerevisiae J. Biol. Chem., April 1, 2005; 280(13): 13084 - 13096. [Abstract] [Full Text] [PDF]