Defined two distinct TOR complexes, only one rapamycin-sensitive, founding the TORC1/TORC2 paradigm.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Yeast S. cerevisiae |
| Journal | Molecular cell |
| Year | 2002 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/s1097-2765(02)00636-6 · PMID 12408816 |
The target of rapamycin (TOR) proteins in Saccharomyces cerevisiae, TOR1 and TOR2, redundantly regulate growth in a rapamycin-sensitive manner. TOR2 additionally regulates polarization of the actin cytoskeleton in a rapamycin-insensitive manner. We describe two functionally distinct TOR complexes. TOR Complex 1 (TORC1) contains TOR1 or TOR2, KOG1 (YHR186c), and LST8. TORC2 contains TOR2, AVO1 (YOL078w), AVO2 (YMR068w), AVO3 (YER093c), and LST8. FKBP-rapamycin binds TORC1, and TORC1 disruption mimics rapamycin treatment, suggesting that TORC1 mediates the rapamycin-sensitive, TOR-shared pathway. FKBP-rapamycin fails to bind TORC2, and TORC2 disruption causes an actin defect, suggesting that TORC2 mediates the rapamycin-insensitive, TOR2-unique pathway. Thus, the distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling. TORC1 and possibly TORC2 are conserved from yeast to man.
| Intervention | Genetic/biochemical (TOR1/TOR2 complexes) |
| Target | TORC1 / TORC2 |
| Model | Yeast (S. cerevisiae) |
| Effect | Defines two TOR complexes: TORC1 (rapamycin-sensitive, growth) and TORC2 (rapamycin-insensitive, actin) |