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PMID: 18235227 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Fission yeast TOR complex 2 activates the AGC-family Gad8 kinase essential for stress resistance and cell cycle control.

Cell cycle (Georgetown, Tex.) ·Vol. 7 ·No. 3 ·2008-02-01 ·Pages 358-64

Ikeda K, Morigasaki S, Tatebe H, Tamanoi F, Shiozaki K

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.

MeSH Terms
Amino Acid Sequence Cell Cycle/genetics,physiology Enzyme Activation/genetics Molecular Sequence Data Oxidative Stress/genetics,physiology Phosphatidylinositol 3-Kinases/genetics,physiology Protein Serine-Threonine Kinases/genetics,metabolism,physiology Schizosaccharomyces/enzymology,genetics Schizosaccharomyces pombe Proteins/biosynthesis,genetics,metabolism,physiology
Chemicals
Rum1 protein, S pombe Schizosaccharomyces pombe Proteins tor2 protein, S pombe Gad8 protein, S pombe Protein Serine-Threonine Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ikeda Kyoko
Section of Microbiology, College of Biological Sciences, University of California, Davis, California, USA.
Morigasaki Susumu
Tatebe Hisashi
Tamanoi Fuyuhiko
Shiozaki Kazuhiro
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Article Info
Journal
Cell cycle (Georgetown, Tex.)
Abbr.
Cell Cycle
ISSN
1551-4005
DOI
10.4161/cc.7.3.5245
Published
2008-02-01
Epub
2007-00-01
Pages
358-64
Language
English
Region
United States
NLM ID
101137841
PMCID
PMC2274895
Subset
IM
Grants
NIGMS NIH HHS · R01 GM059788-09 · United States
NCI NIH HHS · CA41996 · United States
NCI NIH HHS · R01 CA041996 · United States
NIGMS NIH HHS · R01 GM059788 · United States
NIGMS NIH HHS · GM59788 · United States
External Links
PubMed source DOI: 10.4161/cc.7.3.5245 PMC Full Text View journal details
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