Cited by 1,886PI3K/AKT/mTOR signaling in cancerFungal and yeast genetics researchAutophagy in Disease and Therapy

Two TOR Complexes, Only One of which Is Rapamycin Sensitive, Have Distinct Roles in Cell Growth Control

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Loewith, Robbie, Jacinto, Estela, Wullschleger, Stephan, Lorberg, Anja, Crespo, José L., Bonenfant, Débora, Oppliger, Wolfgang, Jenoe, Paul +1 more·2002·Molecular Cell

Abstract

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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Crossref · 10.1016/s1097-2765(02)00636-6

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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.
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
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
  • Health Sciences › Medicine › Epidemiology › 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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