RRC ID 19617
Author Ishiguro J, Shibahara K, Ueda Y, Nakamura K.
Title Fission yeast TOR signaling is essential for the down-regulation of a hyperactivated stress-response MAP kinase under salt stress.
Journal Mol Genet Genomics
Abstract TOR (target of rapamycin) signaling regulates cell growth and division in response to environmental stimuli such as the availability of nutrients and various forms of stress. The vegetative growth of fission yeast cells, unlike other eukaryotic cells, is not inhibited by treatment with rapamycin. We found that certain mutations including pmc1Δ (Ca(2+)-ATPase), cps9-193 (small GTPase, Ryh1) and cps1-12 (1,3-β-D-glucan synthase, Bgs1) confer a rapamycin-sensitive phenotype to cells under salt stress with potassium chloride (>0.5 M). Cytometric analysis revealed that the mutant cells were unable to enter the mitotic cell cycle when treated with the drug under salt stress. Gene cloning and overexpression experiments revealed that the sensitivity to rapamycin was suppressed by the ectopic expression of tyrosine phosphatases, Pyp1 and Pyp2, which are negative regulators of Spc1/Sty1 mitogen-activated protein kinase (MAPK). The level of tyrosine phosphorylation on Spc1 was higher and sustained substantially longer in these mutants than in the wild type under salt stress. The hyperphosphorylation was significantly suppressed by overexpression of pyp1 (+) with concomitant resumption of the mutant cells' growth. In fission yeast, TOR signaling has been thought to stimulate the stress-response pathway, because mutations of TORC2 components such as Tor1, Sin1 and Ste20 result in similar sensitive phenotypes to environmental stress. The present study, however, strongly suggests that TOR signaling is required for the down-regulation of a hyperactivated Spc1 for reentry into the mitotic cell cycle. This finding may shed light on our understanding of a new stress-responsive mechanism in TOR signaling in higher organisms.
Volume 288(1-2)
Pages 63-75
Published 2013-2-1
DOI 10.1007/s00438-012-0731-7
PMID 23271606
MeSH Fungal Proteins / genetics Fungal Proteins / metabolism Gene Expression Regulation, Fungal / drug effects Glucosyltransferases / genetics Glucosyltransferases / metabolism Mitogen-Activated Protein Kinases / metabolism* Monomeric GTP-Binding Proteins / genetics Monomeric GTP-Binding Proteins / metabolism Mutation Phenotype Phosphorylation Plasma Membrane Calcium-Transporting ATPases / genetics Plasma Membrane Calcium-Transporting ATPases / metabolism Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism Salt Tolerance* / genetics Schizosaccharomyces / drug effects Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Signal Transduction* Sirolimus / pharmacology Stress, Physiological* / genetics TOR Serine-Threonine Kinases / metabolism*
IF 2.797
Times Cited 6
Yeast genome library (pTN-L1) L972 L975 JY741 JY746