(A) The protein complexes mTORC1 and mTORC2 regulate cellular processes and growth via phosphorylation of substrate proteins mediated by the mTOR kinase domain. mTORC1 signaling (left) is stimulated by growth factors and amino acids, and is inhibited by low cellular energy levels and hypoxia (a shortage of oxygen). Conserved protein regions involved in target recognition in mTORC1 are located in the Raptor subunit (highlighted in orange). mTORC2 signaling (right) is activated by growth factors and the substrate binding domain identified by Tatebe et al. – the 'Conserved region in the middle' (CRIM) domain – is located in the SIN1 subunit (orange). Prominent downstream targets for each complex are indicated, including mTORC2 targets from the AGC kinase family: SGK1, AKT and PKCα. (B) The human SIN1 protein (top) and its fission yeast ortholog Sin1 (bottom) share similar domain organizations. The CRIM domain is involved in target recognition in both mTORC2 and TORC2. The variable N-terminal domain (which is to the left of the CRIM domain) has been implicated in SIN1/Sin1’s association with other constituents of mTORC2/TORC2. mLST8: mammalian lethal with SEC13 protein 8; PH: pleckstrin-homology; PIKK: phosphoinositide-3-kinase-related kinase; Raptor: regulatory-associated protein of mTOR; RB: (Raf-like) RAS-binding; Rictor: rapamycin-insensitive companion of mTOR; Sin1/SIN1: stress-activated map kinase-interacting protein 1.