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 .

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 RRAGA RRAGB RRAGC RRAGD	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 TSC1 TSC2	Tuberous sclerosis
VHL	Von Hippel-Lindau tumor suppressor

mTORC2 Complex

Symbol	Name
AKT AKT1 AKT2 AKT3	v-akt murine thymoma viral oncogene homolog
FOXO	Forkhead box O
GBL/mLST8	MTOR associated protein; LST8 homolog
GSK3 GSK3A GSK3B	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 Catalytic Subunits PIK3CA PIK3CB PIK3CD PIK3CG Regulatory Subunits PIK3R1 PIK3R2 PIK3R3 PIK3R4 PIK3R5 PIK3R6	Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic and regulatory subunits - Class I
PKC PKC alpha PKC beta PKC delta PKC epsilon PKC gamma PKC eta PKC iota PKC theta PKC zeta	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

Resources

• Cancer Pathway ORF Kit(Sabatini & Wood)

• Tackling Cancers’ Drug Resistance with a New Screening Kit(from David Sabatini & Kris Wood)

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 .