[Show abstract][Hide abstract] ABSTRACT: In eukaryotic organisms, stress-activated mitogen-activated protein kinases (MAPK) play crucial roles in transmitting environmental signals to regulate gene expression for cellular stress adaptation. Here we report that, in the fission yeast Schizosaccharomyces pombe, Spc1/Sty1 MAPK and the Atf1 transcription factor regulate the stress-induced expression of Pmp3, a ubiquitous small membrane protein implicated in the modulation of the plasma membrane potential. The pmp3 null mutant, as well as the spc1 and atf1 mutants, is hypersensitive to the cationic antibiotic hygromycin B. Transcriptional regulation of the Pmp3-like genes by the stress-activated MAPK may also be conserved in other eukaryotes, including plants.
[Show abstract][Hide abstract] 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 Ca2+. 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 Ca2+. 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 Ca2+ but not Na+ and Li+. We propose that Spc1 SAPK and Hal4 kinase cooperatively function to protect cells from the toxic cations.