title: TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Basel, Switzerland.
authors.forename: S B
authors.initials: SB
authors.lastname: Helliwell
authors.forename: P
authors.initials: P
authors.lastname: Wagner
authors.forename: J
authors.initials: J
authors.lastname: Kunz
authors.forename: M
authors.initials: M
authors.lastname: Deuter-Reinhard
authors.forename: R
authors.initials: R
authors.lastname: Henriquez
authors.forename: M N
authors.initials: MN
authors.lastname: Hall
mesh_terms: 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
chemical_list: 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