Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase part of two distinct signaling complexes, mTORC1 and mTORC2. These two complexes share four proteins (mTOR, mLST8, DEPTOR, Tti1/tel2), with only mTORC1 containing Raptor and PRAS40 and mTORC2 containing Rictor, mSin1 and Protor1/2. The complex mTORC1 (rapamycin sensitive complex) coordinates inputs from growth factors, stress, energy status, oxygen and amino acids levels to control processes such as protein and lipid synthesis and autophagy. The complex mTORC2 is insensitive to nutrients and rapamycin, but it responds to insulin signaling. It also controls ion transport and cell shape by targeting serum/glucocorticoid protein kinase (SGK1) and protein kinase (PKC-α) respectively.

The canonical regulation of mTORC1 occurs through the TSC/Rheb pathway which receives signals from AKT, AMPK and IKKβ to activate the complex. Phosphorylation of mTOR at Ser2448 is carried out directly by AKT kinase as well as p70S6 kinase acting as a feedback signal. Phosphorylation at this site is a biomarker for the activation state of the PI-3 kinase pathway as well as the activation status of mTOR. Activation of mTOR leads to phosphorylation of PRAS40, raptor and DEPTOR and the consequential activation of mTORC1. Deregulated signaling of mTOR has been implicated in diseases such as cancer, metabolic syndrome, neurodegeneration and aging. Constitutive activation of PI3K-mTORC1 signaling in cancer cells inhibits autophagy, deregulates protein synthesis via 4E-BP1/eIF4E and increases de novo lipid synthesis via SREBP1. Similarly mTOR signaling is a key factor in the regulation of tissue metabolism in the normal and nutrient overload state affecting the hypothalamus, adipose tissue, the liver, skeletal muscle and pancreas.Notably, rat and human mTOR are 99.5% and 98.9% identical to mouse mTOR, respectively.

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