Figure 1.

Regulation of key cellular processes by mTORC1 and mTORC2. The mTOR signaling pathway comprises mTORC1 and mTORC2, which together promote anabolism, growth, and proliferation. mTORC1 is activated by various signals including growth factors and nutrient availability in the form of amino acids and glucose. The downstream processes regulated by mTORC1 include induction of protein synthesis, mRNA processing, and metabolic rewiring toward de novo nucleotide synthesis, lipogenesis, and oxidative PPP. mTORC2 is only activated by growth factors such as insulin, and its best-characterized substrate is AKT, which is a key activator of glucose and lipid metabolism. More recently, essential roles for other kinases such as PKCs and SGKs downstream of mTORC2 have been defined—such as increased bioactive eicosanoid and arachidonic acid metabolism—which provide compensatory signals that drive cell proliferation. Activating and inhibitory phosphorylation events are denoted by an arrowhead or blunt ended lines, respectively. Abbreviations: TSC1/2, tuberous sclerosis complex 1/2; Rag, Ras-related GTPase; RHEB, Ras homolog enriched in brain; Rap1, Ras-related protein 1; HIF, hypoxia inducible factor; PKM2, pyruvate kinase isozyme M2; PPP, pentose phosphate pathway; SREBP, sterol-regulatory element binding protein; CAD, carbamoyl phosphate synthetase 2; WTAP, Wilms’ tumor 1 associated protein; SRPK2, SR protein kinase 2; ACLY, ATP-citrate lyase; HK, hexokinase; SGK1, serum and glucocorticoid-induced protein kinase-1; PKC, protein kinase C; cPLA2, cytosolic phospholipase A2; NADK, NAD kinase.