The fission yeast mitotic regulator win1+ encodes an MAP kinase kinase kinase that phosphorylates and activates Wis1 MAP kinase kinase in response to high osmolarity.
The Schizosaccharomyces pombe win1-1 mutant has a defect in the G2-M transition of the cell cycle. Although the defect is suppressed by wis1+ and wis4+, which are components of a stress-activated MAP kinase pathway that links stress response and cell cycle control, the molecular identity of Win1 has not been known. We show here that win1+ encodes a polypeptide of 1436 residues with an apparent molecular size of 180 kDa and demonstrate that Win1 is a MAP kinase kinase kinase that phosphorylates and activates Wis1. Despite extensive similarities between Win1 and Wis4, the two MAP kinase kinase kinases have distinct functions. Wis4 is able to compensate for loss of Win1 only under unstressed conditions to maintain basal Wis1 activity, but it fails to suppress the osmosignaling defect conferred by win1 mutations. The win1-1 mutation is a spontaneous duplication of 16 nucleotides, which leads to a frameshift and production of a truncated protein lacking the kinase domain. We discuss the cell cycle phenotype of the win1-1 cdc25-22 wee1-50 mutant and its suppression by wis genes.
Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
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Samejima
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Mackie
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Warbrick
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Weisman
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Fantes
D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics; D002874:Chromosome Mapping; D004789:Enzyme Activation; D005800:Genes, Fungal; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D009994:Osmolar Concentration; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015183:Restriction Mapping; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C109170:win1 protein, S pombe; C109169:wis4 protein, S pombe; D020929:Mitogen-Activated Protein Kinase Kinases; C072068:wis1 protein, S pombe