Abstract
Ca2+/calmodulin-dependent phosphoprotein phosphatase (calcineurin, PP2B) of Saccharomyces cerevisiae is implicated in adaptation to high-salt conditions. Calcineurin mediates high salt-induced expression of the ENA1/PMR2 gene encoding the P-type ATPase, which is suggested to be involved in Na+ efflux. We identified the PDE1 gene encoding the low-affinity cAMP phosphodiesterase as a multicopy suppressor of the Li(+)- and Na(+)-sensitive calcineurin null mutant, suggesting that cAMP is a negative regulator of adaptation to high-salt stress. Genetic analysis indicated that calcineurin and cAMP act antagonistically in a common pathway for adaptation. The bcy1 disruption, which leads to constitutive cAMP-dependent protein kinase (PKA) activity inhibited high NaCl-induced expression of the ENA1/PMR2 gene, caused an elevation of the intracellular Na+ level and a growth defect in high-NaCl medium, all of which were analogous to the defects of a calcineurin mutant. A reduced cAMP level resulting from multiple copies of the PDE1 gene caused increased expression of the ENA1/PMR2 gene in response to high NaCl. We propose a model for the regulation of cation homeostasis, in which calcineurin antagonizes PKA to activate transcription of the ENA1/PMR2 gene in response to high-salt conditions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / isolation & purification
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Adaptation, Physiological / physiology*
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Adenosine Triphosphatases / isolation & purification
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Calcineurin
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Calmodulin-Binding Proteins / genetics
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Calmodulin-Binding Proteins / metabolism*
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Cation Transport Proteins*
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Cations
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / genetics
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Cyclic Nucleotide Phosphodiesterases, Type 1
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Gene Expression Regulation, Fungal
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Genes, Suppressor
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Homeostasis
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Lithium / pharmacology*
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Mutation
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Phosphoprotein Phosphatases / genetics
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Phosphoprotein Phosphatases / metabolism*
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Phosphoric Diester Hydrolases*
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / physiology*
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Saccharomyces cerevisiae Proteins*
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Sodium / pharmacology*
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Sodium-Potassium-Exchanging ATPase
Substances
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Calmodulin-Binding Proteins
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Cation Transport Proteins
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Cations
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ENA1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Lithium
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Sodium
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Calcineurin
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Phosphoprotein Phosphatases
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Phosphoric Diester Hydrolases
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 1
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Adenosine Triphosphatases
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Sodium-Potassium-Exchanging ATPase