RRC ID 12518
Author Ikeda K, Morigasaki S, Tatebe H, Tamanoi F, Shiozaki K.
Title Fission yeast TOR complex 2 activates the AGC-family Gad8 kinase essential for stress resistance and cell cycle control.
Journal Cell Cycle
Abstract Members of the mitogen-activated protein kinase (MAPK) subfamily responsive to environmental stress stimuli are known as SAPKs (stress-activated protein kinases), which are conserved from yeast to humans. In the fission yeast Schizosaccharomyces pombe, Spc1/Sty1 SAPK is activated by diverse forms of stress, such as osmostress, oxidative stress and heat shock, and induces gene expression through the Atf1 transcription factor. Sin1 (SAPK interacting protein 1) was originally isolated as a protein that interacts with Spc1, and its orthologs were also found in diverse eukaryotes. Here we report that Sin1 is not required for the stress gene expression regulated by Spc1 and Atf1, and that Sin1 is an essential component of TOR (target of rapamycin) complex 2 (TORC2). TORC2 is not essential for cell viability in S. pombe but plays important roles in cellular survival of stress conditions through phosphorylation and activation of an AGC-family protein kinase, Gad8. In addition, inactivation of Gad8 results in a synthetic growth defect with cdc25-22, a temperature-sensitive mutation of the Cdc25 phosphatase that activates Cdc2 kinase at G(2)/M. Gad8 also positively regulates expression of the CDK inhibitor gene rum1+, which is essential for cell cycle arrest in G(1) after nitrogen starvation. These results strongly suggest that the TORC2-Gad8 pathway has multiple physiological functions in cellular stress resistance and cell cycle progression at both G(1)/S and G(2)/M transitions.
Volume 7(3)
Pages 358-64
Published 2008-2-1
DOI 10.4161/cc.7.3.5245
PII 5245
PMID 18235227
PMC PMC2274895
MeSH Amino Acid Sequence Cell Cycle / genetics Cell Cycle / physiology* Enzyme Activation / genetics Molecular Sequence Data Oxidative Stress / genetics Oxidative Stress / physiology* Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / physiology* Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism* Protein-Serine-Threonine Kinases / physiology Schizosaccharomyces / enzymology* Schizosaccharomyces / genetics Schizosaccharomyces pombe Proteins / biosynthesis Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Schizosaccharomyces pombe Proteins / physiology
IF 3.259
Times Cited 43
Yeast ?