title: Heat stress activates fission yeast Spc1/StyI MAPK by a MEKK-independent mechanism.
abstract: Fission yeast Spc1/StyI MAPK is activated by many environmental insults including high osmolarity, oxidative stress, and heat shock. Spc1/StyI is activated by Wis1, a MAPK kinase (MEK), which is itself activated by Wik1/Wak1/Wis4, a MEK kinase (MEKK). Spc1/StyI is inactivated by the tyrosine phosphatases Pyp1 and Pyp2. Inhibition of Pyp1 was recently reported to play a crucial role in the oxidative stress and heat shock responses. These conclusions were based on three findings: 1) osmotic, oxidative, and heat stresses activate Spc1/StyI in wis4 cells; 2) oxidative stress and heat shock activate Spc1/StyI in cells that express Wis1AA, in which MEKK consensus phosphorylation sites were replaced with alanine; and 3) Spc1/StyI is maximally activated in Deltapyp1 cells. Contrary to these findings, we report: 1) Spc1/StyI activation by osmotic stress is greatly reduced in wis4 cells; 2) wis1-AA and Deltawis1 cells have identical phenotypes; and 3) all forms of stress activate Spc1/StyI in Deltapyp1 cells. We also report that heat shock, but not osmotic or oxidative stress, activate Spc1 in wis1-DD cells, which express Wis1 protein that has the MEKK consensus phosphorylation sites replaced with aspartic acid. Thus osmotic and oxidative stress activate Spc1/StyI by a MEKK-dependent process, whereas heat shock activates Spc1/StyI by a novel mechanism that does not require MEKK activation or Pyp1 inhibition.
authors.affiliation: Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: K
authors.initials: K
authors.lastname: Shiozaki
authors.forename: M
authors.initials: M
authors.lastname: Shiozaki
authors.forename: P
authors.initials: P
authors.lastname: Russell
mesh_terms: D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins; D017124:Conserved Sequence; D004789:Enzyme Activation; D018869:Heat-Shock Response / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009997:Osmotic Pressure; D018384:Oxidative Stress; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D012694:Serine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins; D013912:Threonine; D012694:Serine; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020930:MAP Kinase Kinase Kinases; C109169:wis4 protein, S pombe; D017027:Protein Tyrosine Phosphatases; C097097:pyp1 protein, S pombe