Fig. 1

mTORC1 and its signaling networks. mTORC1 is composed of mTOR, Raptor, mLST8, PRAS40, Deptor and Tti1/Tel2 complex. The signaling networks of mTORC1. a Growth factors, such as insulin, stimulation leads to the activation of classic PI3K-AKT-TSC2-mTORC1 pathway. b Amino acids, mainly leucine and arginine, stimulate mTORC1 through GTP-loaded RAG. c LATS can trigger hippo pathway by inhibition of YAP to activate mTORC1 signaling through PTEN suppression. d WNT signaling stimulates mTORC1 by inhibiting the activation of GSK3β, which can phosphorylate TSC2. e Notch signaling can regulate mTOR activity in liver. f AMPK inhibits mTORC1 activity through phosphorylating TSC2 or Raptor under energy limitation. Upon various stimulation, mTORC1 modulates its substrates such as 4E-BP, ULK1, TFEB1, LIPIN1, HIF1α, ATF4. S6K and GRB10 to affect cellular proliferation, metabolism and many other biological processes. In addition, negative feedback mechanisms of mTOR substrates, in turn, fine-tune mTORC1 signaling networks. For examples, Grb10 negatively regulates the mTORC1 signaling pathway through a phosphorylation-dependent feedback mechanism on reptor or IRS. And S6K1 also negatively accommodates phosphorylation of IRS-1 to suppress IRS-1/PI3K /Akt /mTOR signaling. Akt, protein kinase B; AMPK, 5’AMP- activated protein kinase; ATF4, activating transcription factor 4; Deptor, DEP domain-containing mTOR-interacting protein; GRB10, growth factor receptor-bound protein 10; GSK3β, glycogen synthase kinase 3β; HIF1α, hypoxia inducible factor-1α; IRS, insulin receptor substrate; LATS, large tumour suppressor homologue kinase; mLST8, mammalian lethal with SEC13 protein 8; mTORC1, mammalian or mechanistic target of rapamycin complex1; PDK1, Phosphoinositide-dependent kinase-1; PI3K, phosphoinositide 3-kinase; PRAS40, Akt/PKB substrate 40 kDa; PTEN, phosphatase and tensin homolog; RAG, RAS-related GTP-binding Protein; Raptor, regulatory associated protein of mTOR; RHEB, RAS homolog enriched in brain; S6K, ribosomal S6 kinase; TFEB1, transcription factor EB; TSC1, tuberous sclerosis complex 1; TSC2, tuberous sclerosis complex 2; ULK1, UNC-like kinase 1; YAP, Yes-associated protein; 4E-BP, eIF4E-binding protein