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Two TOR Complexes, Only One of which Is Rapamycin Sensitive, Have Distinct Roles in Cell Growth Control
Open accessAbstract
The target of rapamycin (TOR) proteins in Saccharomyces cerevisiae, TOR1 and TOR2, redundantly regulate growth in a rapamycin-sensitive manner. TOR2 additionally regulates polarization of the actin cytoskeleton in a rapamycin-insensitive manner. We describe two functionally distinct TOR complexes. TOR Complex 1 (TORC1) contains TOR1 or TOR2, KOG1 (YHR186c), and LST8. TORC2 contains TOR2, AVO1 (YOL078w), AVO2 (YMR068w), AVO3 (YER093c), and LST8. FKBP-rapamycin binds TORC1, and TORC1 disruption mimics rapamycin treatment, suggesting that TORC1 mediates the rapamycin-sensitive, TOR-shared pathway. FKBP-rapamycin fails to bind TORC2, and TORC2 disruption causes an actin defect, suggesting that TORC2 mediates the rapamycin-insensitive, TOR2-unique pathway. Thus, the distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling. TORC1 and possibly TORC2 are conserved from yeast to man.
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“specifically, mTORC2 contains the mTOR, Rictor, LST8 and SIN1 proteins (Loewith et al., 2002).”
From Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities (2021) · cites this paper as Loewith et al., 2002
In the citing paper
“which was discovered after it was shown that rapamycin is able to inhibit mTORC1 via binding to the protein FKBP12 (REFS31,32).”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [31]
In the citing paper
“mTOR is present in two complexes, mTORC1 (associated with ‘raptor’) and mTORC2 (associated with ‘rictor’), accounting for the diversity, specificity and selectivity of rapamycin-mediated inhibition of TOR signalling”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [31]
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Metadata
- Authors
- Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., & Hall, M. N.
- Affiliations
- University of Basel (CH)
- Corresponding author
- Hall, Michael N.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2002-09
- Volume
- 10
- Issue
- 3
- Pages
- 457-468
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2152600551
- Cited by
- 1,886
- References
- 59
- Citations by year
- 2026: 37 · 2025: 47 · 2024: 68 · 2023: 65 · 2022: 75 · 2021: 79 · 2020: 70 · 2019: 76 · 2018: 76 · 2017: 100 · 2016: 68 · 2015: 115 · 2014: 97 · 2013: 103 · 2012: 135
- FWCI
- 15.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- TOR signaling, TOR1, TOR2, rapamycin sensitivity, cell growth regulation, LST8, Saccharomyces cerevisiae
- MeSH terms
- Actins, Animals, Antifungal Agents, Cell Line, Cytoskeleton, Fungal Proteins, Glycogen, Humans, Protein Binding, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Tissue Distribution, Signal Transduction, Phosphotransferases (Alcohol Group Acceptor), Genes, Reporter, Cell Cycle Proteins, Phosphatidylinositol 3-Kinases, Sirolimus, Tacrolimus Binding Proteins, Drug Resistance, Fungal, Saccharomyces cerevisiae Proteins, Macromolecular Substances
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