TOR controls transcriptional and translational programs via Sap-Sit4 protein phosphatase signaling effectors.
The Tor kinases are the targets of the immunosuppressive drug rapamycin and couple nutrient availability to cell growth. In the budding yeast Saccharomyces cerevisiae, the PP2A-related phosphatase Sit4 together with its regulatory subunit Tap42 mediates several Tor signaling events. Sit4 interacts with other potential regulatory proteins known as the Saps. Deletion of the SAP or SIT4 genes confers increased sensitivity to rapamycin and defects in expression of subsets of Tor-regulated genes. Sap155, Sap185, or Sap190 can restore these responses. Strains lacking Sap185 and Sap190 are hypersensitive to rapamycin, and this sensitivity is Gcn2 dependent and correlated with a defect in translation, constitutive eukaryotic initiation factor 2alpha hyperphosphorylation, induction of GCN4 translation, and hypersensitivity to amino acid starvation. We conclude that Tor signals via Sap-Sit4 complexes to control both transcriptional and translational programs that couple cell growth to amino acid availability.
Rohde
John R
JR
Department of Molecular Genetics and Microbiology, Duke University Medical Center, 322 CARL Bldg., Box 3546, Research Dr., Durham, NC 27710, USA.
Campbell
Susan
S
Zurita-Martinez
Sara A
SA
Cutler
N Shane
NS
Ashe
Mark
M
Cardenas
Maria E
ME
D048868:Adaptor Proteins, Signal Transducing; D005786:Gene Expression Regulation / Q000502:physiology; D017930:Genes, Reporter; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D019869:Phosphatidylinositol 3-Kinases; D010749:Phosphoprotein Phosphatases; D010750:Phosphoproteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D011494:Protein Kinases; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases; D017413:Ribonucleoprotein, U2 Small Nuclear; D029701:Saccharomyces cerevisiae Proteins; C491800:SAP155 protein, S cerevisiae; C083324:TOR1 protein, S cerevisiae; C512912:GCN2 protein, S cerevisiae; C104343:SIT4 protein, S cerevisiae