TOR signalling in bugs, brain and brawn

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Abstract
The target of rapamycin (TOR) signalling pathway is a central controller of cell growth. TOR is a highly conserved kinase. It is a member of the phosphatidylinositol kinase-related protein kinase (PIKK) family. It contains HEAT repeats, a FAT domain, an FRB domain and a catalytic domain. TOR forms a complex with several proteins. In yeast, there are two TOR complexes (TORC1 and TORC2). TORC1 contains TOR1 or TOR2 and the evolutionarily conserved proteins KOG1 and LST8. TORC1 mediates the signalling pathways that control rapamycin-sensitive, growth-related processes in response to nutrients. TORC2 contains TOR2, AVO1, AVO2, AVO3, and LST8. TORC2 mediates the signalling pathway that controls actin cytoskeleton organization. Mammalian TOR (mTOR) forms a complex with raptor (mKOG1) and mLST8, and is known as the nutrient-sensitive complex. TOR controls translation, protein stability and transcription in both yeast and mammals. In yeast, TOR is regulated by nutrients. In mammals, mTOR is regulated by nutrients and growth factors such as insulin. mTOR and the insulin signalling pathways converge on S6K and 4E-BP. Amino acids and growth factors might signal to TOR by inhibiting the TSC complex. TOR regulates protein phosphatases. The regulation of phosphatases by TOR ensures a rapid and coordinated response to nutrient deprivation. Studies of the TOR signalling pathway in Drosophila highlight the role of this pathway in the control of cell and organism size. mTOR also controls the growth of non-proliferating cells, such as neurons and muscles, by the control of translation.