mTOR

Supporting information

mTOR (mechanistic Target Of Rapamycin, mammalian Target Of Rapamycin aka FRAP, FK506 binding protein 12 (FKBP12)-rapamycin associated protein 1) plays a key role in coordinating the signals for a number of pathways, including insulin signaling, nutrient sensing and mitogenic signaling. mTOR is a large (>280kD), multidomain protein that includes a kinase domain and a FKBP12 binding domain. Rapamycin binds to FKBP12 and then complexes with mTOR to inhibit the enzyme.

The PI 3-K pathway regulates mTOR via the tuberous sclerosis proteins, TSC1 and TSC2. These proteins activate the small GTPase Rheb, that in turn binds and activates the kinase domain of mTOR. In cells, mTOR exists as two large complexes: mTORC1 and mTORC2. mTORC1 includes several proteins, including the regulatory protein Raptor and mTORC2 includes the regulatory protein Rictor. Only mTORC1 is rapamycin sensitive. Upstream signals regulating mTORC1 include growth factors, and glucose and oxygen levels. The most widely known phosphorylation targets of mTORC1 are the key components of the protein translation machinery, 4E-BP and p70 S6 kinase 1(S6K1). A key role of mTORC2 is actin organization, although mTORC2 can phosphorylate and activate Akt. Serum glucocorticoid-induced protein kinase 1 (SGK1) has been recently identified as an mTORC2 substrate. mTORC2 is not as sensitive to nutrient levels as mTORC1, and is insensitive to rapamycin.

mTORC1 is a sensor of nutrient and growth factor levels. Consequently, it has been linked to autophagy and other metabolic pathways. mTORC1 inhibits autophagy in the presence of nutrients; under conditions such as those resulting from starvation, infection, or oxidative stress, mTORC1 is inhibited and autophagy is triggered. AMPK also inhibits mTORC1 in response to glucose deprivation. mTORC1 has also been associated with glycolysis, and sterol and lipid biosynthesis. Its regulation of SREBP-1 (sterol regulatory element binding protein 1) and HIF (hypoxia-inducible factor) is suggestive of a role for mTORC1 in cellular mechanisms balancing nutrient sensing with carbohydrate and lipid metabolism.

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Species Gene Symbol Gene Accession No. Protein Accession No.
Human MTOR NM_004958 P42345
Mouse Mtor NM_020009 Q9JLN9
Rat Mtor NM_019906 P42346

Literature for mTOR

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Request copy | Download PDF | View all Product Guides & Listings
Cancer Research Product Guide
Kinases Product Listing

A collection of over 400 products for kinase research, the listing includes inhibitors of:

  • Receptor Tyrosine Kinases
  • Protein Kinases A, C, D and G
  • PI-3 Kinase, Akt and mTOR
  • MAPK Signaling
  • Receptor Serine/Threonine Kinases
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Kinases Product Listing
Pain Research Product Guide

A collection of over 250 products for pain research, the guide includes research tools for the study of:

  • Nociception
  • Ion Channels
  • G-Protein-Coupled Receptors
  • Intracellular Signaling
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Pain Research Product Guide
Angiogenesis Life Science Poster

Written by Yongping Crawford and Napoleone Ferrara, this poster highlights major targets for antiangiogenic therapy, namely tumor- and stromal cell-derived pathways. Intrinsic and acquired resistance are described; antiangiogenic therapies targeting the VEGF pathway are also summarized. Compounds available from Tocris are listed.

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Angiogenesis Life Science Poster
mTOR Signaling Pathway
mTOR Signaling Pathway

mTOR is a serine/threonine kinase that nucleates at multiprotein complexes mTORC1 and mTORC2. Signaling by these complexes regulates cell growth, proliferation and survival.

View pathway | Download PDF

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Cancer Research Product Guide

Cancer Research Product Guide

Our Cancer Research Guide highlights over 750 products for cancer research. Request copy or view PDF today.

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Kinase Inhibitor Toolbox

80 Kinase inhibitors
pre-dissolved in DMSO

Kinase Inhibitor Toolbox

Includes many of the latest kinase inhibitors to become commercially available. Covers a wide range of kinase targets including EGFR, MAPK and CDK.

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Kinases Product Listing

Kinases Product Listing

Our Kinase listing highlights over 400 products for kinase research. Request copy or view PDF today.

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Pain Research Product Guide

Pain Research Product Guide

Our Pain guide highlights over 280 products for Pain research. Request copy or view PDF today.

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VEGF Pathway & Anti-Angiogenic Therapy

Written by N. Ferrara & Y. Crawford

Angiogenesis Life Science Poster

A summary of antiangiogenic therapies targeting the VEGF pathway and the mechanisms of therapy resistance. Request copy today.

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mTOR Pathway

mTOR Signaling Pathway

The mTOR complexes (mTORC1 and 2) respond to intra- and extracellular signals to mediate cell growth, proliferation and survival. View pathway or download PDF today.

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