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PMID: 12077316 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Pheromone induction promotes Ste11 degradation through a MAPK feedback and ubiquitin-dependent mechanism.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 14 ·2002-07-09 ·Pages 9160-5

Esch RK, Errede B

Abstract

Ste11 is the mitogen-activated protein kinase (MAPK) kinase kinase in the MAPK cascades that mediate mating, high osmolarity glycerol, and filamentous growth responses in Saccharomyces cerevisiae. We show stimulation of the mating pathway by pheromone promotes an accelerated turnover of Ste11 through a MAPK feedback and ubiquitin-dependent mechanism. This degradation is pathway specific, because Ste11 is stable during activation of the high osmolarity glycerol pathway. Because the steady-state amount of Ste11 does not change significantly during pheromone induction, we infer that maintenance of MAPK activation involves repeated cycles in which naive Ste11 is activated and then targeted for degradation. This model predicts that elimination of active Ste11 would rapidly curtail MAPK activation upon attenuation of the upstream signal. This prediction is confirmed by the finding that blocking ubiquitin-dependent Ste11 degradation during pheromone induction abolishes the characteristic attenuation profile for MAPK activation.

MeSH Terms
Enzyme Stability Feedback Glycerol/metabolism MAP Kinase Kinase Kinases/metabolism Mitogen-Activated Protein Kinases/metabolism Models, Biological Osmolar Concentration Pheromones/biosynthesis Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/metabolism Signal Transduction Ubiquitin/metabolism
Chemicals
Pheromones Saccharomyces cerevisiae Proteins Ubiquitin FUS3 protein, S cerevisiae Mitogen-Activated Protein Kinases MAP Kinase Kinase Kinases Ste11 protein, S cerevisiae Glycerol
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Esch R K
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Errede B
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.142034399
Published
2002-07-09
Epub
2002-00-20
Pages
9160-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC123111
Subset
IM
Grants
NIGMS NIH HHS · GM-39582 · United States
External Links
PubMed source DOI: 10.1073/pnas.142034399 PMC Full Text View journal details
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