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The Yeast Sks1p Kinase Signaling Network Regulates Pseudohyphal Growth and Glucose Response


Eukaryotic cells respond to nutritional and environmental stress through complex regulatory programs controlling cell metabolism, growth, and morphology. In the budding yeast Saccharomyces cerevisiae, conditions of limited nitrogen and/or glucose can initiate a dramatic growth transition wherein the yeast cells form extended multicellular filaments resembling the true hyphal tubes of filamentous fungi. The formation of these pseudohyphal filaments is governed by core regulatory pathways that have been studied for decades; however, the mechanism by which these signaling systems are integrated is less well understood. We find that the protein kinase Sks1p contributes to the integration of signals for nitrogen and/or glucose limitation, resulting in pseudohyphal growth. We implemented a mass spectrometry-based approach to profile phosphorylation events across the proteome dependent upon Sks1p kinase activity and identified phosphorylation sites important for mitochondrial function and pseudohyphal growth. Our studies place Sks1p in the regulatory context of a well-known pseudohyphal growth signaling pathway. We further find that SKS1 is conserved and required for stress-responsive colony morphology in the principal opportunistic human fungal pathogen Candida albicans. Thus, Sks1p is part of the mechanism integrating glucose-responsive cell signaling and pseudohyphal growth, and its function is required for colony morphology linked with virulence in C. albicans.


Vyšlo v časopise: The Yeast Sks1p Kinase Signaling Network Regulates Pseudohyphal Growth and Glucose Response. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004183
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004183

Souhrn

Eukaryotic cells respond to nutritional and environmental stress through complex regulatory programs controlling cell metabolism, growth, and morphology. In the budding yeast Saccharomyces cerevisiae, conditions of limited nitrogen and/or glucose can initiate a dramatic growth transition wherein the yeast cells form extended multicellular filaments resembling the true hyphal tubes of filamentous fungi. The formation of these pseudohyphal filaments is governed by core regulatory pathways that have been studied for decades; however, the mechanism by which these signaling systems are integrated is less well understood. We find that the protein kinase Sks1p contributes to the integration of signals for nitrogen and/or glucose limitation, resulting in pseudohyphal growth. We implemented a mass spectrometry-based approach to profile phosphorylation events across the proteome dependent upon Sks1p kinase activity and identified phosphorylation sites important for mitochondrial function and pseudohyphal growth. Our studies place Sks1p in the regulatory context of a well-known pseudohyphal growth signaling pathway. We further find that SKS1 is conserved and required for stress-responsive colony morphology in the principal opportunistic human fungal pathogen Candida albicans. Thus, Sks1p is part of the mechanism integrating glucose-responsive cell signaling and pseudohyphal growth, and its function is required for colony morphology linked with virulence in C. albicans.


Zdroje

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