title: Protein phosphatase 2C acts independently of stress-activated kinase cascade to regulate the stress response in fission yeast.
abstract: Stress-activated signal transduction pathways, which are largely conserved among a broad spectrum of eukaryotic species, have a crucial role in the survival of many forms of stress. It is therefore important to discover how these pathways are both positively and negatively regulated. Recent genetic studies have implicated protein phosphatase 2C (PP2C) as a novel negative regulator of stress response pathways in both budding and fission yeasts. Moreover, it was hypothesized that PP2C dephosphorylates one or more components of protein kinase cascades that are at the core of stress-activated signal transduction pathways. Herein we present genetic and biochemical studies of the fission yeast Schizosaccharomyces pombe that disprove this hypothesis and indicate that PP2C instead negatively regulates a downstream element of the pathway. First, high expression of PP2C produces phenotypes that are inconsistent with negative regulation of the Wik1-Wis1-Spc1 stress-activated kinase cascade. Second, high expression of PP2C leads to sustained activating tyrosine phosphorylation of Spc1. Third, Spc1-dependent phosphorylation of Atf1, a transcription factor substrate of Spc1, is unaffected by high expression of PP2C. Fourth, high expression of PP2C suppresses Atf1-dependent transcription of a stress-response gene. These studies strongly suggest that PP2C acts downstream of Spc1 kinase in the stress-activated signal transduction pathway.
authors.affiliation: Departments of Molecular Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: F
authors.initials: F
authors.lastname: Gaits
authors.forename: K
authors.initials: K
authors.lastname: Shiozaki
authors.forename: P
authors.initials: P
authors.lastname: Russell
mesh_terms: D051697:Activating Transcription Factor 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D015966:Gene Expression Regulation, Fungal; D020930:MAP Kinase Kinase Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D008954:Models, Biological; D009154:Mutation; D009997:Osmotic Pressure; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012331:RNA, Fungal / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051697:Activating Transcription Factor 1; D004268:DNA-Binding Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D011494:Protein Kinases; 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; D020929:Mitogen-Activated Protein Kinase Kinases; C087358:PTC1 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000071636:Protein Phosphatase 2C; D017027:Protein Tyrosine Phosphatases