TOR1 AND TOR2 ARE STRUCTURALLY AND FUNCTIONALLY SIMILAR BUT NOT IDENTICAL PHOSPHATIDYLINOSITOL KINASE HOMOLOGS IN YEAST

The Saccharomyces cerevisiae genes TOR1 and TOR2 were originally ident ified by mutations that confer resistance to the immunosuppressant rap amycin. TOR2 was previously shown to encode an essential 282-kDa phosp hatidylinositol 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 co nfers a cell cycle (G1) arrest as does exposure to rapamycin; disrupti on of TOR2 alone is lethal but does not cause a cell cycle arrest. TOR 1-TOR2 and TOR2-TOR1 hybrids indicate that carboxy-terminal domains of TOR1 and TOR2 containing a lipid kinase sequence motif are interchang eable and therefore functionally equivalent; the other portions of TOR 1 and TOR2 are not interchangeable. The TOR1-1 and TOX2-1 mutations, w hich confer rapamycin resistance, alter the same potential protein kin ase 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 c omponents of a novel signal transduction pathway controlling progressi on through G1.