mTOR Signaling Pathway

The mechanistic target of rapamycin (mTOR) is a highly conserved atypical serine/threonine protein kinase. mTORC interacts with other proteins to form two multi-protein complexes, the mTOR complex (mTORC) 1 and mTORC2. Both complexes contain mLST8/GβL and DEPTOR. mTORC1 also contains Raptor and PRAS40 proteins, wherein Raptor interacts with the target of rapamycin signaling (TOS) motifs of mTOR substrates in a rapamycin-sensitive manner to activate this complex. Contrastingly, mTORC2 also contains Rictor, mSIN1, and Protor1/2, and the functional activity of mTORC2 is dependent on Rictor and mSIN1. mTOR signaling can be activated by upstream signals including growth factors (e.g., Insulin, IGF1), cellular stress, metabolism/energy state (e.g., O₂ and ATP/ADP), amino acid nutrients (e.g., Leucine and Arginine), and neurotransmitters (e.g., Neuropeptides and Glutamate). mTOR signaling controls several fundamental biological processes including translation and turnover of proteins, lipid and glucose metabolism, cellular growth, proliferation, survival, autophagy, cytoskeleton organization, etc. Aberrant mTOR signaling has been linked to the pathophysiology of diseases like cancer, cardiovascular disease, and diabetes.