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cell dish icon mTOR Pathway


The mechanistic or mammalian target of rapamycin (mTOR) is a key metabolic regulator controlling cell growth and proliferation. mTOR, a serine/threonine kinase, is found in two complexes, mTORC1 and mTORC2. Each complex contains a unique subunit: raptor for mTORC1, and rictor for mTORC2.

Background

mTORC1 & mTORC2

The better-characterized mTORC1 responds to various signals, including amino acids, stress, oxygen, energy levels, and growth factors. mTORC1 integrates these signals to determine the nutritional state of the cell and regulates the switch from anabolic to catabolic processes. Active mTORC1 promotes protein and lipid synthesis, and increases energy production through glycolysis to fuel these energy-intensive processes. mTORC1 also blocks catabolic processes including autophagy and lysosome biogenesis.

mTORC2 does not respond to nutrients, but it is activated by growth factors, including insulin. mTORC2 influences cell survival and cytoskeletal organization.

Cancer Impact

Enhanced signaling through either mTORC1 or mTORC2 correlates with poor prognosis in many cancers, including breast, colon, ovarian, and liver cancers. mTORC1 is activated downstream of PI3K/Akt and MAPK/ERK, both of which are commonly dysregulated in cancer. Loss of the tumor suppressor p53 also promotes aberrant mTORC1 activity, and multiple familial cancers are caused by inactivating mutations in negative regulators of mTORC1. The hyperactivation of mTORC1 in cancer promotes the conditions needed for uncontrolled cell growth and proliferation, including an abundant supply of macromolecules and energy, as well as the presence of both pro-proliferative and anti-apoptotic signals. mTORC2, which appears to signal upstream of Akt, also promotes cell survival and proliferation.

mTOR Pathway Plasmids

Click on a name to find available plasmids for the gene, or browse the gene list below. For multiple isoforms or subunits, individual links to each gene page are provided below. Color is used for clarity and does not indicate a specific relationship.

The content for this page was generated with the help of David Sabatini .

mTOR Pathway

Color is used for clarity and does not indicate a specific relationship.

The content for this page was generated with the help of David Sabatini .

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mTOR Pathway - Gene List

Click on a name to find available plasmids for the gene. For components with multiple isoforms or subunits, individual links to each gene page are provided below.

mTORC1 Complex

Symbol Name
4E-BP Eukaryotic translation initiation factor 4E, binding protein 1
Cyclin D1 Also known as CCND1
eIF-4E Eukaryotic translation initiation factor 4E
GBL/mLST8 MTOR associated protein; LST8 homolog
LKB1 Also known as STK11; serine/threonine kinase 11
mTOR Mechanistic target of rapamycin
NF1 Neurofibromin 1
PRAS40 Also known as AKT1S1; AKT1 substrate 1 (proline rich)
PTEN Phosphatase and tensin homolog
Rag Ras-related GTP binding
Raptor Also known as RPTOR; Regulatory associated protein of MTOR, complex 1
Rheb Ras homolog enriched in brain
S6K Also known as RPS6KB1; Ribosomal protein S6 kinase B1
TSC1/2 Tuberous sclerosis
VHL Von Hippel-Lindau tumor suppressor

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mTORC2 Complex

Symbol Name
AKT v-akt murine thymoma viral oncogene homolog
FOXO Forkhead box O
GBL/mLST8 MTOR associated protein; LST8 homolog
GSK3 Glycogen synthase kinase 3
MDM2 MDM2 proto-oncogene
mSin1 Also known as MAPKAP1; Mitogen-activated protein kinase associated protein 1
mTOR Mechanistic target of rapamycin
p53 TP53; tumor protein p53
PDK1 Pyruvate dehydrogenase kinase, isozyme 1
PI3K Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic and regulatory subunits - Class I
PKC Protein kinase C
Protor Also known as PRR5; proline rich 5
PTEN Phosphatase and tensin homolog
Rictor RPTOR independent companion of MTOR, complex 2
SGK Serum/glucocorticoid regulated kinase 1

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Resources

References

mTOR signaling in growth control and disease. Laplante M, Sabatini DM. Cell. 2012 Apr 13;149(2):274-93. doi: 10.1016/j.cell.2012.03.017. PubMed PMID: 22500797 .

Rapamycin: one drug, many effects. Li J, Kim SG, Blenis J. Cell Metab. 2014 Mar 4;19(3):373-9. doi: 10.1016/j.cmet.2014.01.001. PubMed PMID: 24508508 .

Targeting the translation machinery in cancer. Bhat M, Robichaud N, Hulea L, Sonenberg N, Pelletier J, Topisirovic I. Nat Rev Drug Discov. 2015 Apr;14(4):261-78. doi: 10.1038/nrd4505. PubMed PMID: 25743081 .