Abstract
The regulation of electrical membrane potential is a fundamental property of living cells. This biophysical parameter determines nutrient uptake, intracellular potassium and turgor, uptake of toxic cations, and stress responses. In fungi and plants, an important determinant of membrane potential is the electrogenic proton-pumping ATPase, but the systems that modulate its activity remain largely unknown. We have characterized two genes from Saccharomyces cerevisiae, PTK2 and HRK1 (YOR267c), that encode protein kinases implicated in activation of the yeast plasma membrane H(+)-ATPase (Pma1) in response to glucose metabolism. These kinases mediate, directly or indirectly, an increase in affinity of Pma1 for ATP, which probably involves Ser-899 phosphorylation. Ptk2 has the strongest effect on Pma1, and ptk2 mutants exhibit a pleiotropic phenotype of tolerance to toxic cations, including sodium, lithium, manganese, tetramethylammonium, hygromycin B, and norspermidine. A plausible interpretation is that ptk2 mutants have a decreased membrane potential and that diverse cation transporters are voltage dependent. Accordingly, ptk2 mutants exhibited reduced uptake of lithium and methylammonium. Ptk2 and Hrk1 belong to a subgroup of yeast protein kinases dedicated to the regulation of plasma membrane transporters, which include Npr1 (regulator of Gap1 and Tat2 amino acid transporters) and Hal4 and Hal5 (regulators of Trk1 and Trk2 potassium transporters).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Amino Acid Transport Systems
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cations / metabolism
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Cations / pharmacology
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Cell Membrane / chemistry*
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Cell Membrane / drug effects
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Cell Membrane / metabolism*
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Cloning, Molecular
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Enzyme Activation
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Focal Adhesion Protein-Tyrosine Kinases
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Glucose / metabolism
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Glucose / pharmacology
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Hygromycin B / pharmacology
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Isoenzymes
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Kinetics
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Lithium / metabolism
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Lithium / pharmacology
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Membrane Potentials / drug effects
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Mutation / genetics
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Phosphorylation
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Phosphoserine / metabolism
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Potassium Channels / genetics
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Potassium Channels / metabolism
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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Proton-Translocating ATPases / chemistry
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Proton-Translocating ATPases / genetics
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Proton-Translocating ATPases / metabolism*
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Saccharomyces cerevisiae / cytology
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Saccharomyces cerevisiae / enzymology*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
Substances
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Amino Acid Transport Systems
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Carrier Proteins
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Cations
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Fungal Proteins
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Isoenzymes
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PMA2 protein, S cerevisiae
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Potassium Channels
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Saccharomyces cerevisiae Proteins
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Phosphoserine
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Hygromycin B
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Adenosine Triphosphate
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Lithium
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Protein Kinases
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Protein-Tyrosine Kinases
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Focal Adhesion Protein-Tyrosine Kinases
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HRK1 protein, S cerevisiae
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Protein Serine-Threonine Kinases
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PMA1 protein, S cerevisiae
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Proton-Translocating ATPases
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Glucose