mTOR Signaling Pathway

The mammalian Target of Rapamycin (mTOR) Complex is the central cellular regulator of anabolic and catabolic cellular metabolism and survival. mTOR forms at least two distinct multi-protein complexes (mTORCs) with additional regulatory proteins. mTORC1 includes mTOR, Raptor, Pras40, Deptor, and GBL/mLST8 while mTORC2 includes mTOR, Rictor, mSin1, Proctor/PRR5, Deptor, and GBL/mLST8. mTOR activity is regulated in response to both extracellular and intracellular cues. Extracellular signaling factors, including Wnts, TNF-alpha, and growth factors, signal through a variety of intracellular pathways to TSC1/2, to regulate mTORC1 activity. In addition to responding to extracellular cues, mTORC1 activity is also regulated by intracellular cues including energy availability, oxygen levels, and amino acid availability. In the presence of available amino acids, the mTOR Complex 1 (mTORC1) is recruited to the lysosomal membrane where it initiates anabolic activities including protein synthesis, lipid synthesis, autophagy, and mitochondrial metabolism and biogenesis.

Less is known about the upstream signals and cellular functions that regulate mTORC2. mTORC2 activity is strongly correlated with AKT activity. mTORC2 has been shown to regulate cytoskeletal rearrangement, as well as cell survival and proliferation.