title: The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle.
abstract: The fission yeast Sty1 MAP kinase is required for cell cycle control, initiation of sexual differentiation, and protection against cellular stress. Like the mammalian JNK/SAPK and p38/CSBP1 MAP kinases, Sty1 is activated by a range of environmental insults including osmotic stress, hydrogen peroxide, menadione, heat shock, and the protein synthesis inhibitor anisomycin. We have identified an upstream regulator that mediates activation of the Sty1 MAP kinase by multiple environmental stresses as the product of the mitotic catastrophe suppressor, mcs4. Mcs4 is structurally and functionally homologous to the budding yeast SSK1 response regulator, suggesting that the eukaryotic stress-activated MAP kinase pathway is controlled by a conserved two-component system. Mcs4 acts upstream of Wak1, a homolog of the SSK2 and SSK22 MEK kinases, which transmits the stress signal to the Wis1 MEK. We show that the Wis1 MEK is controlled by an additional pathway that is independent of both Mcs4 and the Wak1 MEK kinase. Furthermore, we demonstrate that Mcs4 is required for the correct timing of mitotic initiation by mechanisms both dependent and independent on Sty1, indicating that Mcs4 coordinately controls cell cycle progression with the cellular response to environmental stress.
authors.affiliation: Division of Yeast Genetics, National Institute for Medical Research, The Ridgeway, London, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Shieh
authors.forename: M G
authors.initials: MG
authors.lastname: Wilkinson
authors.forename: V
authors.initials: V
authors.lastname: Buck
authors.forename: B A
authors.initials: BA
authors.lastname: Morgan
authors.forename: K
authors.initials: K
authors.lastname: Makino
authors.forename: J B
authors.initials: JB
authors.lastname: Millar
mesh_terms: D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015183:Restriction Mapping; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D013696:Temperature
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C105788:Mcs4 protein, S pombe; C087199:SSK1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020930:MAP Kinase Kinase Kinases; C109169:wis4 protein, S pombe; D020929:Mitogen-Activated Protein Kinase Kinases; C072068:wis1 protein, S pombe