Fission yeast TOR complex 2 activates the AGC-family Gad8 kinase essential for stress resistance and cell cycle control.
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.
Ikeda
Kyoko
K
Section of Microbiology, College of Biological Sciences, University of California, Davis, California, USA.
Morigasaki
Susumu
S
Tatebe
Hisashi
H
Tamanoi
Fuyuhiko
F
Shiozaki
Kazuhiro
K
D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation / Q000235:genetics; D008969:Molecular Sequence Data; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D029702:Schizosaccharomyces pombe Proteins; C086077:Rum1 protein, S pombe; C513100:tor2 protein, S pombe; C476401:Gad8 protein, S pombe