Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression.
The yeast TOR2 gene encodes an essential 282 kd phosphatidylinositol (PI) 3-kinase homolog. TOR2 is related to the catalytic subunit of bovine PI 3-kinase and to yeast VPS34, a vacuolar sorting protein also shown to have PI 3-kinase activity. The immunosuppressant rapamycin most likely acts by inhibiting PI kinase activity because TOR2 mutations confer resistance to rapamycin and because a TOR1 TOR2 double disruption (TOR1 is a nonessential TOR2 homolog) confers G1 arrest, as does rapamycin. Our results further suggest that 3-phosphorylated phosphoinositides, whose physiological significance has not been determined, are an important signal in cell cycle activation. In yeast, this signal may act in a signal transduction pathway similar to the interleukin-2 signal transduction pathway in T cells.
Department of Biochemistry, University of Basel, Switzerland.
J
J
Kunz
R
R
Henriquez
U
U
Schneider
M
M
Deuter-Reinhard
N R
NR
Movva
M N
MN
Hall
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D015825:Chromosomes, Fungal; D003001:Cloning, Molecular; D004271:DNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D016193:G1 Phase / Q000187:drug effects; D005800:Genes, Fungal; D015698:Genomic Library; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D019869:Phosphatidylinositol 3-Kinases; D010770:Phosphotransferases / Q000235:genetics* / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor); D010957:Plasmids; D011090:Polyenes / Q000494:pharmacology*; D012331:RNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D020123:Sirolimus
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D007166:Immunosuppressive Agents; D009838:Oligodeoxyribonucleotides; D019869:Phosphatidylinositol 3-Kinases; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011090:Polyenes; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; C081135:TOR2 protein, S cerevisiae