Fig. 2

A The upstream pathway of mTORC1 and mTORC2. Growth factor, cytokines, or TLR signaling activates PI3K, which in turn activates AKT. The AMPK, LKB1, and IRS are also involved in regulating mTORC1 and mTORC2. TLR, Toll-like receptor; PI3K, phosphatidylinositol-3-OH kinase; AKT, RAC-α serine/threonine-protein kinase; TSC, tuberous sclerosis complex; Rheb, Ras homolog enriched in the brain; PTEN, phosphatase and tensin homolog deleted on chromosome 10; PIP2, ephosphatidylinositol-3,4-bisphosphate; PIP3, phosphatidylinositol-3,4,5-triphosphate; AMPK, the mitogen-activated protein kinase; LKB1, liver kinase B1, IRS, insulin receptor substrate. B The downstream pathway of mTORC1. mTORC1 activates S6K1 and eIF4E to promote protein synthesis and cell growth. mTORC1 also inhibits 4E-BP1 to initiate translation. Additionally, mTORC1 influences PDCD4, SKAR, ATF4, MTHFD2, CAD, HIF1α, ULK1, and TFEB to regulate glucose metabolism, lipid synthesis, and autophagy. S6K1, S6 kinase 1; eIF4E, eukaryotic translation initiation factor 4E; eIF4B, eukaryotic translation initiation factor 4B; 4E-BP1, the eIF4E binding protein 1; PDCD4, programmed cell death protein 4; SKAR, S6K1 Aly/REF-like target; ATF4, activating transcription factor 4; MTHFD2, methylenetetrahydrofolate dehydrogenase 2; CAD, carbamoyl-phosphate synthetase; HIF1α, hypoxia-inducible factor-1α; ULK1, unc-51-like kinase1; TFEB, transcription factor EB. C The downstream pathway of mTORC2. mTORC2 activates SGK1 and PKCα, which play roles in cell survival and cytoskeletal organization. SGK1, serum and glucocorticoid inducible kinase 1; PKCα, protein kinase C-α