Figure 1. The mTOR signaling pathway.

The key signaling pathway that regulates mTORC1 and mTORC2 is depicted above. mTOR is activated by signaling through the PI3K pathway, regulating cell growth, and proliferation. PTEN, TSC1, and TSC2 act as negative regulators of the mTOR pathway and inhibition of the aforementioned leads to hyperactivation of mTOR. mTOR1 signaling requires activation of the adaptor protein raptor and mTORC2, which is insensitive to acute rapamycin treatment, requires activation of rictor protein. Multiple signals from growth factors, amino acids, cellular energy status, and stress are integrated into mTORC1. Activated mTORC1 plays a major role in promoting cell growth and proliferation by stimulating various anabolic processes including protein, lipid, nucleotide synthesis, and ribosome biogenesis, and inhibiting catabolic processes such as autophagy. mTORC2 is regulated by growth factors and although mechanisms are poorly defined, it has been linked to cytoskeleton.

Abbv: IRS1:Insulin Receptor substrate 1; mTOR: mammalian target of rapamycin; PDK1: 3-phosphoinositide-dependent protein kinase 1; PTEN: Phosphatase and tensin homolog; PI3K: Phosphoinositide 3-kinase; TSC1: TSC Complex Subunit 1; TSC2 TSC Complex Subunit 2; RHEB: Ras homolog enriched in brain; S6K1: Ribosomal protein S6 kinase beta-1; eIF4: Eukaryotic initiation factor 4F; 4E-BP1: eIF4E-binding protein.