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PMID: 17804815 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A single MAPKKK regulates the Hog1 MAPK pathway in the pathogenic fungus Candida albicans.

Molecular biology of the cell ·Vol. 18 ·No. 11 ·2007-11-00 ·Pages 4603-14

Cheetham J, Smith DA, da Silva Dantas A, Doris KS, Patterson MJ, Bruce CR, Quinn J

Abstract

The Hog1 mitogen-activated protein kinase (MAPK) plays a central role in stress responses in the human pathogen Candida albicans. Here, we have investigated the MAPK kinase kinase (MAPKKK)-dependent regulation of the pathway. In contrast to the Hog1 pathway in Saccharomyces cerevisiae, which is regulated by three MAPKKKs (Ssk2, Ssk22, and Ste11), our results demonstrate that Hog1 in C. albicans is regulated by a single MAPKKK Ssk2. Deletion of SSK2 results in comparable stress and morphological phenotypes exhibited by hog1Delta cells, and Ssk2 is required for the stress-induced phosphorylation and nuclear accumulation of Hog1, and for Hog1-dependent gene expression. Furthermore, phenotypes associated with deletion of SSK2 can be circumvented by expression of a phosphomimetic mutant of the MAPKK Pbs2, indicating that Ssk2 regulates Hog1 via activation of Pbs2. In S. cerevisiae, the Hog1 pathway is also regulated by the MAPKKK Ste11. However, we can find no connection between Ste11 and the regulation of Hog1 in C. albicans. Furthermore, expression of a chimeric Pbs2 protein containing the Ste11-dependent regulatory region of S. cerevisiae Pbs2, fails to stimulate Ste11-dependent stress signaling in C. albicans. Collectively, our data show that Ssk2 is the sole MAPKKK to relay stress signals to Hog1 in C. albicans and that the MAPK signaling network in C. albicans has diverged significantly from the corresponding network in S. cerevisiae.

MeSH Terms
Candida albicans/enzymology,pathogenicity Gene Deletion MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases/genetics,metabolism Mitogen-Activated Protein Kinases/genetics,metabolism Mutation/genetics Phenotype Phosphorylation Protein Binding
Chemicals
Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Cheetham Jill
Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom.
Smith Deborah A
da Silva Dantas Alessandra
Doris Kathryn S
Patterson Miranda J
Bruce Catherine R
Quinn Janet
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e07-06-0581
Published
2007-11-00
Epub
2007-00-05
Pages
4603-14
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2043575
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · BB/C510383/1 · United Kingdom
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1091/mbc.e07-06-0581 PMC Full Text View journal details
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