title: Response of fission yeast to toxic cations involves cooperative action of the stress-activated protein kinase Spc1/Sty1 and the Hal4 protein kinase.
abstract: Stress-activated protein kinases (SAPKs), members of a mitogen-activated protein kinase (MAPK) subfamily, are highly conserved among eukaryotes. Studies of yeasts demonstrated that SAPKs play pivotal roles in survival responses to high osmolarity, oxidative stress, and heat shock. Here we report a novel physiological role of the fission yeast Spc1 SAPK in cellular resistance to certain cations, such as Na(+), Li(+), and Ca(2+). Strains lacking Spc1 or its activator, Wis1 MAPK kinase, are hypersensitive to these cations. Spc1 positively regulates expression of sod2(+) encoding a Na(+)/H(+) antiporter through Atf1 and other transcription factors. In addition, we have identified a novel Spc1-interacting protein, Hal4, which is highly homologous to the budding yeast Sat4/Hal4 protein kinase. Like its budding yeast counterpart, the fission yeast Hal4 kinase is essential for cellular resistance to Na(+), Li(+), and Ca(2+). The hal4-null phenotype is complemented by overexpression of the Trk1 potassium transporter or increased K(+) in the growth medium, suggesting that Hal4 promotes K(+) uptake, which consequently increases cellular resistance to other cations. Interestingly, the Spc1-Hal4 interaction appears to be required for cellular resistance to Ca(2+) but not Na(+) and Li(+). We propose that Spc1 SAPK and Hal4 kinase cooperatively function to protect cells from the toxic cations.
authors.affiliation: Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616, USA.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Wang
authors.forename: Koichi
authors.initials: K
authors.lastname: Shimada
authors.forename: Masayo
authors.initials: M
authors.lastname: Morishita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiozaki
mesh_terms: D051697:Activating Transcription Factor 1; D000595:Amino Acid Sequence; D002412:Cations / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D025141:Drug Resistance, Fungal; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051697:Activating Transcription Factor 1; D002412:Cations; D004268:DNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; C501077:Sod2 protein, S pombe; D017923:Sodium-Hydrogen Exchangers; D014157:Transcription Factors; D011494:Protein Kinases; C501076:Hal4 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D011188:Potassium