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

Lookup NU author(s): Jill Cheetham, Alessandra da Silva Dantas, Dr Miranda Morton, Dr Catherine Bruce, Professor Janet Quinn

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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 hog1Δ 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. © 2007 by The American Society for Cell Biology.


Publication metadata

Author(s): Cheetham J, Smith DA, da Silva Dantas A, Doris KS, Patterson MJ, Bruce CR, Quinn J

Publication type: Article

Publication status: Published

Journal: Molecular Biology of the Cell

Year: 2007

Volume: 18

Issue: 11

Pages: 4603-4614

Print publication date: 01/11/2007

Online publication date: 05/09/2007

Date deposited: 20/09/2010

ISSN (print): 1059-1524

ISSN (electronic): 1939-4586

Publisher: American Society for Cell Biology

URL: http://dx.doi.org/10.1091/mbc.E07-06-0581

DOI: 10.1091/mbc.E07-06-0581

PubMed id: 17804815


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