MAPKKK-independent Regulation of the Hog1 Stress-activated Protein Kinase in Candida albicans*
| Autor: | Susan Scorfield, Kathryn S. Doris, Donna M. MacCallum, Alessandra da Silva Dantas, Deborah A. Smith, Frank C. Odds, Janet Quinn, Jill Cheetham |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Osmosis
Stress-activated Protein Kinases Saccharomyces cerevisiae Proteins Virulence Pathogenesis Biology medicine.disease_cause Biochemistry Gene Expression Regulation Enzymologic 03 medical and health sciences Mice Bacterial Proteins Gene Expression Regulation Fungal Candida albicans medicine Animals Mitogen-Activated Protein Kinase 8 Phosphorylation Protein kinase A Molecular Biology Alleles 030304 developmental biology Stress Response 0303 health sciences Mutation Mice Inbred BALB C MAP kinase kinase kinase 030306 microbiology Fungi Cell Biology biology.organism_classification MAP Kinase Kinase Kinases Molecular biology Corpus albicans Yeast Disease Models Animal Mutagenesis Female Signal transduction Mitogen-Activated Protein Kinases Protein Kinases Signal Transduction |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | The Hog1 stress-activated protein kinase regulates both stress responses and morphogenesis in Candida albicans and is essential for the virulence of this major human pathogen. Stress-induced Hog1 phosphorylation is regulated by the upstream MAPKK, Pbs2, which in turn is regulated by the MAPKKK, Ssk2. Here, we have investigated the role of phosphorylation of Hog1 and Pbs2 in Hog1-mediated processes in C. albicans. Mutation of the consensus regulatory phosphorylation sites of Hog1 (Thr-174/Tyr-176) and Pbs2 (Ser-355/Thr-359), to nonphosphorylatable residues, resulted in strains that phenocopied hog1Δ and pbs2Δ cells. Consistent with this, stress-induced phosphorylation of Hog1 was abolished in cells expressing nonphosphorylatable Pbs2 (Pbs2(AA)). However, mutation of the consensus sites of Pbs2 to phosphomimetic residues (Pbs2(DD)) failed to constitutively activate Hog1. Furthermore, Ssk2-independent stress-induced Hog1 activation was observed in Pbs2(DD) cells. Collectively, these data reveal a previously uncharacterized MAPKKK-independent mechanism of Hog1 activation in response to stress. Although Pbs2(DD) cells did not exhibit high basal levels of Hog1 phosphorylation, overexpression of an N-terminal truncated form of Ssk2 did result in constitutive Hog1 activation, which was further increased upon stress. Significantly, both Pbs2(AA) and Pbs2(DD) cells displayed impaired stress resistance and attenuated virulence in a mouse model of disease, whereas only Pbs2(AA) cells exhibited the morphological defects associated with loss of Hog1 function. This indicates that Hog1 mediates C. albicans virulence by conferring stress resistance rather than regulating morphogenesis. |
| Databáze: | OpenAIRE |
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