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. 2022 Mar 18;14(6):1555. doi: 10.3390/cancers14061555

Figure 2.

Figure 2

The cellular signaling and regulation of the mTOR pathway. Structurally, mTORC1 and mTORC2 share several protein components, including mTOR kinase, DEPTOR, and mLST8. Each complex also contains a couple of unique proteins. RAPTOR and PRSA40 are the components of mTORC1, where RICTOR and mSIN1 are the subunits of mTORC2. Both complexes integrate extracellular signaling through upstream PI3K/AKT and Ras/Raf/Mek/Erk signaling pathways to guide their own activation. mTORC1 is also regulated by the cellular status of amino acids, hypoxia, energetic stress, and DNA damage while mTORC2 mainly responds to growth factors. IRS, insulin receptor substrate; PI3K, phosphoinositide 3-kinases; PIP2, phosphatidylinositol (4,5)-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; PTEN, phosphatase and tensin homologue; PDK1, phosphoinositide-dependent protein kinase-1; AKT, protein kinase B; mTOR, mammalian target of rapamycin; RAPTOR, regulatory-associated protein of mTOR; DEPTOR, DEP-domain-containing mTOR-interacting protein; PRAS40, proline-rich AKT substrate 40 kDa; mLST8, mammalian lethal with SEC13 protein 8; RICTOR, rapamycin-insensitive companion of mammalian target of rapamycin; PROTOR1/2, protein associated with rictor 1 or 2; mSIN1, MAPK-interacting protein 1; TSC1/TSC2, tuberous sclerosis complex 1, 2; Rheb, Ras homolog enriched in brain; AMPK, AMP-activated protein kinase; GATOR1/2, GAP activity towards the Rags 1,2; LKB1, liver kinase B1; Ras, rat sarcoma kinase; RAF, rapidly accelerated fibrosarcoma kinase; ERK, extracellular signal-regulated kinases, Mek, MAPK/ERK kinase; EGFR, epidermal growth factor receptor; REDD1, regulated in development and DNA damage responses 1.