InterPro domain: IPR026683

This entry represents the serine/threonine-protein kinase TOR (target of rapamycin), which was first identified by mutations in yeast that confer resistance to the growth inhibitory properties of rapamycin [ 1 ]. TOR proteins are structurally and functionally conserved in all eukaryotes examined. However, yeasts contain two Tor proteins (Tor1 and Tor2), while higher eukaryotes such as humans possess a single TOR protein [ 2 ]. They are central regulators of cellular metabolism, growth and survival in response environmental signals [ 3 , 4 , 5 ].

In budding yeast, the Tor2 protein exists in two distinct multi-component complexes, TORC1 and TORC2. TORC1 regulates cell growth by regulating many growth-related processes and is rapamycin sensitive, while TROC2 regulates the cell cytoskeleton and is rapamycin insensitive. Budding yeast TORC1 consists of either Tor1 or Tor2 in complex with Kog1, Lst8 and Tco89, while TORC2 is composed of Avo1, Avo2, Tsc11, Lst8, Bit61, Slm, Slm2 and Tor2 [ 6 , 7 ]. In both yeast and mammals, FKBP12-rapamycin binds to Tor (Tor1, Tor2, or mTOR) in TORC1, but not to Tor (Tor2 or mTOR) in TORC2. It has been suggested that the architecture of TORC2 or its unique composition might be responsible for the observed rapamycin resistance [ 8 ].

1. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253, 905-9
2. Molecular Basis of the Rapamycin Insensitivity of Target Of Rapamycin Complex 2. Mol. Cell
3. TOR controls translation initiation and early G1 progression in yeast. Mol. Biol. Cell 7, 25-42
4. The fission yeast TOR homolog, tor1+, is required for the response to starvation and other stresses via a conserved serine. J. Biol. Chem. 276, 7027-32
5. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110, 163-75
6. Ubiquitin regulates TORC1 in yeast Saccharomyces cerevisiae. Mol. Microbiol. 58, 977-88
7. The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol. Biol. Cell 16, 1883-900