Figure 1.

The mechanistic target of rapamycin (mTOR) signaling pathway. Rapamycin is an acute inhibitor of mTOR complex 1 (mTORC1), which phosphorylates substrates including S6 kinase 1 (S6K1), eIF4E-binding protein 1 (4E-BP1), transcription factor EB (TFEB), unc-51-like autophagy-activating kinase 1 (Ulk1), and growth factor receptor-bound protein 10 (GRB-10). Rapamycin dosed chronically also inhibits mTOR complex 2 (mTORC2), which regulates the phosphorylation of Akt, serum/glucocorticoid regulated kinase (SGK), and members of the protein kinase C (PKC) family. mTORC2 is primarily responsive to insulin/insulin-like growth factor 1 (IGF-1) signaling, whereas mTORC1 is sensitive to insulin as well as amino acids and glucose. AMPK, Adenosine monophosphate-stimulated kinase.