Eukaryotic Cell doi:10.1128/EC.00349-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.
Ssk2 MAPKKK governs divergent patterns of the stress-activated Hog1 signaling pathway in Cryptococcus neoformans
Yong-Sun Bahn,
Scarlett Geunes-Boyer,
and
Joseph Heitman*
Department of Bioinformatics and Life Science, Soongsil University, Seoul, Korea; Departments of Cell Biology, Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
* To whom correspondence should be addressed. Email:
heitm001{at}duke.edu.
 |
Abstract |
|---|
The stress-activated p38/Hog1 MAPK pathway is structurally conserved in many organisms as diverse as yeast and mammals and modulates myriad cellular functions. The Hog1 pathway is uniquely specialized to control differentiation and virulence factors in a majority of clinical Cryptococcus neoformans serotype A and D strains. Here we identified and characterized the Ssk2 MAPKKK that functions upstream of the MAPKK Pbs2 and the MAPK Hog1 in C. neoformans. The SSK2 gene was identified as a potential component responsible for differential Hog1 phosphorylation between the serotype D f1 sibling strains B-3501 and B-3502 through comparative analysis of their meiotic map with meiotic segregation of Hog1-dependent sensitivity to the antifungal drug fludioxonil. Ssk2 is the only component of the Hog1 MAPK cascade that is polymorphic between the two strains, and the B-3501 and B-3502 SSK2 alleles were distinguished by two coding sequence changes. Supporting this finding, SSK2 allele exchange completely interchanged their Hog1 controlled signaling patterns, related phenotypes, and virulence between strains B-3501 and JEC21. In the serotype A strain H99, disruption of the SSK2 gene enhanced capsule and melanin biosynthesis and mating efficiency, similar to pbs2 and hog1 mutations. Furthermore, ssk2
, pbs2, and hog1 mutants were hypersensitive to a variety of stresses and resistant to fludioxonil. In agreement with these results, Hog1 phosphorylation was abolished in the ssk2 mutant, similar to the pbs2 mutant. Taken together, these findings indicate that Ssk2 is a critical interface connecting the two-component system and the Pbs2-Hog1 MAPK pathway in C. neoformans.
