TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast.
The Saccharomyces cerevisiae genes TOR1 and TOR2 were originally identified by mutations that confer resistance to the immunosuppressant rapamycin. TOR2 was previously shown to encode an essential 282-kDa phosphatidylinositol kinase (PI kinase) homologue. The TOR1 gene product is also a large (281 kDa) PI kinase homologue, with 67% identity to TOR2. TOR1 is not essential, but a TOR1 TOR2 double disruption uniquely confers a cell cycle (G1) arrest as does exposure to rapamycin; disruption of TOR2 alone is lethal but does not cause a cell cycle arrest. TOR1-TOR2 and TOR2-TOR1 hybrids indicate that carboxy-terminal domains of TOR1 and TOR2 containing a lipid kinase sequence motif are interchangeable and therefore functionally equivalent; the other portions of TOR1 and TOR2 are not interchangeable. The TOR1-1 and TOR2-1 mutations, which confer rapamycin resistance, alter the same potential protein kinase C site in the respective protein's lipid kinase domain. Thus, TOR1 and TOR2 are likely similar but not identical, rapamycin-sensitive PI kinases possibly regulated by phosphorylation. TOR1 and TOR2 may be components of a novel signal transduction pathway controlling progression through G1.
Helliwell
S B
SB
Department of Biochemistry, University of Basel, Switzerland.
Wagner
P
P
Kunz
J
J
Deuter-Reinhard
M
M
Henriquez
R
R
Hall
M N
MN
D019870:1-Phosphatidylinositol 4-Kinase; D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D004352:Drug Resistance, Microbial / Q000235:genetics; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D005800:Genes, Fungal; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics*; D011090:Polyenes / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D020123:Sirolimus
D019870:1-Phosphatidylinositol 4-Kinase; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011090:Polyenes; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; C083324:TOR1 protein, S cerevisiae; C081135:TOR2 protein, S cerevisiae; C441760:PIK1 protein, S cerevisiae