This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
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
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stratton, H. F.
Right arrow Articles by Stone, D. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stratton, H. F.
Right arrow Articles by Stone, D. E.

 Previous Article  |  Next Article 

Mol. Cell. Biol., 11 1996, 6325-6337, Vol 16, No. 11
Copyright © 1996, American Society for Microbiology

The mating-specific G(alpha) protein of Saccharomyces cerevisiae downregulates the mating signal by a mechanism that is dependent on pheromone and independent of G(beta)(gamma) sequestration

HF Stratton, J Zhou, SI Reed and DE Stone
Laboratory for Molecular Biology, University of Illinois at Chicago 60607, USA.

It has been inferred from compelling genetic evidence that the pheromone-responsive G(alpha) protein of Saccharomyces cerevisiae, Gpa1, directly inhibits the mating signal by binding to its own beta(gamma) subunit. Gpa1 has also been implicated in a distinct but as yet uncharacterized negative regulatory mechanism. We have used three mutant alleles of GPA1, each of which confers resistance to otherwise lethal doses of pheromone, to explore this possibility. Our results indicate that although the G322E allele of GPA1 completely blocks the pheromone response, the E364K allele promotes recovery from pheromone treatment rather than insensitivity to it. This observation suggests that Gpa1, like other G(alpha) proteins, interacts with an effector molecule and stimulates a positive signal--in this case, an adaptive signal. Moreover, the Gpa1-mediated adaptive signal is itself induced by pheromone, is delayed relative to the mating signal, and does not involve sequestration of G(beta)(gamma). The behavior of N388D, a mutant form of Gpa1 predicted to be activated, strongly supports these conclusions. Although N388D cannot sequester beta(gamma), as evidenced by two-hybrid analysis and its inability to complement a Gpa1 null allele under normal growth conditions, it can stimulate adaptation and rescue a gpa1(delta) strain when cells are exposed to pheromone. Considered as a whole, our data suggest that the pheromone-responsive heterotrimeric G protein of S. cerevisiae has a self-regulatory signaling function. Upon activation, the heterotrimer dissociates into its two subunits, one of which stimulates the pheromone response, while the other slowly induces a negative regulatory mechanism that ultimately shuts off the mating signal downstream of the receptor.


This article has been cited by other articles:

  • Strickfaden, S. C., Pryciak, P. M. (2008). Distinct Roles for Two G{alpha} G Interfaces in Cell Polarity Control by a Yeast Heterotrimeric G Protein. Mol. Biol. Cell 19: 181-197 [Abstract] [Full Text]  
  • Wu, Y.-L., Hooks, S. B., Harden, T. K., Dohlman, H. G. (2004). Dominant-negative Inhibition of Pheromone Receptor Signaling by a Single Point Mutation in the G Protein {alpha} Subunit. J. Biol. Chem. 279: 35287-35297 [Abstract] [Full Text]  
  • Blackwell, E., Halatek, I. M., Kim, H.-J. N., Ellicott, A. T., Obukhov, A. A., Stone, D. E. (2003). Effect of the Pheromone-Responsive G{alpha} and Phosphatase Proteins of Saccharomyces cerevisiae on the Subcellular Localization of the Fus3 Mitogen-Activated Protein Kinase. Mol. Cell. Biol. 23: 1135-1150 [Abstract] [Full Text]  
  • Metodiev, M. V., Matheos, D., Rose, M. D., Stone, D. E. (2002). Regulation of MAPK Function by Direct Interaction with the Mating-Specific Galpha in Yeast. Science 296: 1483-1486 [Abstract] [Full Text]  
  • Swift, S., Sheridan, P. J., Covic, L., Kuliopulos, A. (2000). PAR1 Thrombin Receptor-G Protein Interactions. SEPARATION OF BINDING AND COUPLING DETERMINANTS IN THE Galpha SUBUNIT. J. Biol. Chem. 275: 2627-2635 [Abstract] [Full Text]  
  • Apanovitch, D. M., Iiri, T., Karasawa, T., Bourne, H. R., Dohlman, H. G. (1998). Second Site Suppressor Mutations of a GTPase-deficient G-Protein alpha -Subunit. SELECTIVE INHIBITION OF Gbeta gamma -MEDIATED SIGNALING. J. Biol. Chem. 273: 28597-28602 [Abstract] [Full Text]  
  • Li, E., Meldrum, E., Stratton, H. F., Stone, D. E. (1998). Substitutions in the Pheromone-Responsive Gss Protein of Saccharomyces cerevisiae Confer a Defect in Recovery from Pheromone Treatment. Genetics 148: 947-961 [Abstract] [Full Text]  
  • Davis, C., Dube, P., Konopka, J. B. (1998). Afr1p Regulates the Saccharomyces cerevisiae {alpha}-Factor Receptor by a Mechanism That Is Distinct From Receptor Phosphorylation and Endocytosis. Genetics 148: 625-636 [Abstract] [Full Text]  
  • Iiri, T., Farfel, Z., Bourne, H. R. (1997). Conditional activation defect of a human Gsalpha  mutant. Proc. Natl. Acad. Sci. USA 94: 5656-5661 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»