Abstract
Targets of rapamycin (TORs) are conserved phosphatidylinositol kinase-related kinases that are involved in the coordination between nutritional or mitogenic signals and cell growth. Here we report the initial characterization of two Schizosaccharomyces pombe TOR homologs, tor1(+) and tor2(+). tor2(+) is an essential gene, whereas tor1(+) is required only under starvation and other stress conditions. Specifically, Deltator1 cells fail to enter stationary phase or undergo sexual development and are sensitive to cold, osmotic stress, and oxidative stress. In complex with the prolyl isomerase FKBP12, the drug rapamycin binds a conserved domain in TORs, FRB, thus inhibiting some of the functions of TORs. Mutations at a conserved serine within the FRB domain of Saccharomyces cerevisiae TOR proteins led to rapamycin resistance but did not otherwise affect the functions of the proteins. The S. pombe tor1(+) exhibits different features; substitution of the conserved serine residue, Ser(1834), with arginine compromises its functions and has no effect on the inhibition that rapamycin exerts on sexual development in S. pombe.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antifungal Agents / pharmacology
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Arginine / chemistry
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Blotting, Western
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Cell Cycle Proteins
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Cloning, Molecular
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Cold Temperature
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Conserved Sequence
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Drug Resistance
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Epitopes / chemistry
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Flow Cytometry
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Fungal Proteins / chemistry*
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Fungal Proteins / genetics
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Fungal Proteins / physiology*
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Mutation
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Osmosis
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Oxidative Stress
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Peptidylprolyl Isomerase / pharmacology
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Phenotype
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Phosphatidylinositol 3-Kinases*
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Phosphotransferases (Alcohol Group Acceptor) / chemistry*
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / physiology*
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Protein Binding
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Protein Kinases / chemistry*
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Protein Kinases / genetics
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Protein Kinases / physiology*
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Schizosaccharomyces / metabolism
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Schizosaccharomyces pombe Proteins / chemistry*
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Schizosaccharomyces pombe Proteins / genetics
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Schizosaccharomyces pombe Proteins / physiology*
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Serine / chemistry*
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Sirolimus / pharmacology
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Tacrolimus Binding Protein 1A / pharmacology
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Time Factors
Substances
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Antifungal Agents
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Cell Cycle Proteins
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Epitopes
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Fungal Proteins
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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Schizosaccharomyces pombe Proteins
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Serine
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Arginine
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Protein Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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Tor1 protein, S pombe
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TOR1 protein, S cerevisiae
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TOR2 protein, S cerevisiae
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tor2 protein, S pombe
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Tacrolimus Binding Protein 1A
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Peptidylprolyl Isomerase
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Sirolimus