Abstract
Adaptation to environmental stress is critical for cell survival. Adaptation generally occurs via changes in transcription and translation. However, there is a time lag before changes in gene expression, which suggests that more rapid mechanisms likely exist. In this study, we show that in yeast, the cyclin-dependent kinase Pho85/CDK5 provides protection against hyperosmotic stress and acts before long-term adaptation provided by Hog1. This protection requires the vacuolar/endolysosomal signaling lipid PI3,5P2 We show that Pho85/CDK5 directly phosphorylates and positively regulates the PI3P-5 kinase Fab1/PIKfyve complex and provide evidence that this regulation is conserved in mammalian cells. Moreover, this regulation is particularly crucial in yeast for the stress-induced transient elevation of PI3,5P2 Our study reveals a rapid protection mechanism regulated by Pho85/CDK5 via signaling from the vacuole/lysosome, which is distinct temporally and spatially from the previously discovered long-term adaptation Hog1 pathway, which signals from the nucleus.
© 2017 Jin et al.
MeSH terms
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Adaptation, Physiological
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Animals
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Cells, Cultured
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Cyclin-Dependent Kinase 5 / metabolism
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / metabolism*
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Cyclins / genetics
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Cyclins / metabolism
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Endosomes / enzymology*
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Fibroblasts / enzymology
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Humans
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Lysosomes / enzymology*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Microbial Viability
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism
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Mutation
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Osmotic Pressure*
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphatidylinositol Phosphates / metabolism*
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Phosphorylation
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Phosphotransferases / metabolism
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Saccharomyces cerevisiae / enzymology*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism*
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Second Messenger Systems*
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Time Factors
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Up-Regulation
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Vacuoles / enzymology*
Substances
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Cdk5r1 protein, mouse
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Cyclins
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Membrane Proteins
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PHO80 protein, S cerevisiae
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Phosphatidylinositol Phosphates
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Saccharomyces cerevisiae Proteins
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VAC7 protein, S cerevisiae
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phosphatidylinositol 3,5-diphosphate
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Phosphotransferases
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FAB1 protein, S cerevisiae
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Phosphotransferases (Alcohol Group Acceptor)
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PIKFYVE protein, human
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Pikfyve protein, mouse
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Cyclin-Dependent Kinase 5
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CDK5 protein, human
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Cdk5 protein, mouse
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Cyclin-Dependent Kinases
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PHO85 protein, S cerevisiae
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HOG1 protein, S cerevisiae
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Mitogen-Activated Protein Kinases