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. 2021 Jan 29;118(2):424–439. doi: 10.1093/cvr/cvab033

Figure 1.

Figure 1

Overview of mTOR biology. (A) Architecture of mechanistic target of rapamycin (mTOR) complex 1 and 2 (mTORC1-2). (B,C) Molecular mechanisms and substrates modulated by mTORC1 (B) and mTORC2 (C). (D) Schematic representation of mTORC1 activation. mTORC1 activation occurs at the lysosome surface. In response to nutrient signals, Rags is activated (Rag A/B-GTP, Rag C/D-GDP) (1) and mediates mTORC1 translocation to the lysosome surface, in close proximity to RHEB (2). Once at the lysosome, additional inputs (growth factors) are required for RHEB-induced mTORC1 activation (3). (E) Upstream modulators of mTORC1 and mTORC2. Green and red indicate positive and negative regulators of mTOR, respectively. See text for further details. The figure was made using tools provided by Servier Medical Art, among others. Legend: 4E-BP1, eukaryotic translation initiation factor 4E (eIF4E)-binding protein-1; AKT, protein kinase B; AMBRA1, activating molecule in Beclin1-regulated autophagy; AMPK, adenosine monophosphate-activated protein kinase; ATF4, activating transcription factor 4; ATG, autophagy-related gene; CAD, carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase; CASTOR 1-2, cellular arginine sensor for mTORC1 1-2; ERK, extracellular signal-regulated kinase 1/2; GATOR 1-2, GAP activity towards Rags 1-2; DEPTOR, DEP domain-containing mTOR-interacting protein; FKBP12, FK506-binding protein of 12 kDa–rapamycin complex; FLCN, folliculin; GSK3β, glycogen synthase kinase-3β; HIF-1, hypoxia-inducible factor-1α; IKKβ, inhibitor of NF-κB kinase-β; mLST8, mammalian lethal with sec-13 protein 8; mSIN1, mammalian stress-activated protein kinase-interaction protein 1; MST1, mammalian sterile 20-like kinase 1; PI3K, phosphoinositide 3 kinase; PKCα, protein kinase C α; PRAS40, proline-rich AKT substrate 40; PROTOR 1-2, protein observed with RICTOR 1-2; RAG, Ras-related GTPase; RAPTOR, regulatory-associated protein of mTOR; REDD1, regulated in development and DNA damage responses 1; RHEB, Ras homolog enriched in brain; RhoA, Ras homolog gene family, member A; RICTOR, rapamycin-insensitive companion of mTOR; RSK1, p90 ribosomal S6 kinase; S6K1, S6 kinase-1; SGK1, serum and glucocorticoid-induced protein kinase-1; SLC38A9, solute carrier family 38 member 9; SREBP1/2, sterol regulatory element-binding protein 1-2; TEL 1-2, Tel 2 interacting protein 1/2; TFE3, transcription factor E3; TFEB, transcription factor EB; TSC1-2, tuberous sclerosis protein 1/2; ULK1, unc-51-like kinase 1; UVRAG, UV radiation resistance-associated gene; v-ATPase, vacuolar H(+)-adenosine triphosphatase; YY1/PGC-1α, transcription factor yin-yang 1/peroxisome proliferator-activated receptor γ coactivator-1α transcriptional complex.