mTOR (mammalian target of rapamycin) is a member of the ATM (ataxia telangiectasia mutated) -related family of kinases.
Studies of mTOR have demonstrated that it performs an essential role in integrating cellular signals received from growth factors and from the detection of nutrient, stress, and energy levels in the cell.
The integration of signals by mTOR functions to control cell growth by influencing cellular processes such as translation initiation, ribosome biogenesis, and transcription factor localization. mTOR is an evolutionarily conserved protein originally identified as the direct target of the cell cycle arresting activity of the immunosuppressive drug, rapamycin. Through its interaction with FKBP12, rapamycin is able to exert its effects by binding the mTOR Complex1 (mTORC1) and inhibiting the mTOR signaling pathway.
In response to growth and survival signals, mTOR has been shown to directly phosphorylate the ribosomal protein S6 kinase p70 (S6k), the translational inhibitors 4E-BP1 and 4E-BP2, and PHAS; therefore mTOR exerts many of its effects via the control of protein translation.
Biochemical characterization of the mTORC1 complex has identified the mTOR interacting proteins Raptor and Lst8p. A rapamycin-insensitive mTOR complex, mTORC2 has also been identified. This complex does not possess Raptor but another protein termed Rictor (rapamycin insensitive companion of TOR). In addition to Rictor, the mTORC2 complex contains mLST8, mSin1, and protor 1. This complex appears to play a role in the regulation of cytoskeletal organization and has been shown to be the phosphoinositide-dependent protein kinase-2 (PDK2) responsible for AKT activation.
Two negative regulators of mTOR have been identified. The TSC1-TSC2 complex is a heterodimer of the TSC1 and TSC2 gene products responsible for the genetic disorder tuberous sclerosis. The identification of mTOR and the study of its function in yeast, humans, and drosophila have defined the mTOR pathway as a complex central regulator of cell growth. Future studies that focus on the convergence of mTOR signaling with other growth and survival pathways will provide a framework for targeting proteins in the mTOR and related pathways as anti-cancer therapies.
mTOR Product Focus (pdf, 198 kB)
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