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Cited by 2,665PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingHippo pathway signaling and YAP/TAZ

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Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton

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Dos D. Sarbassov, Ali, Siraj M, Kim, Do-Hyung, Guertin, David A, Latek, Robert R, Erdjument-Bromage, Hediye, Tempst, Paul, Sabatini, David M·2004·Current Biology
DOI 10.1016/j.cub.2004.06.054
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Abstract

The mammalian TOR (mTOR) pathway integrates nutrient- and growth factor-derived signals to regulate growth, the process whereby cells accumulate mass and increase in size. mTOR is a large protein kinase and the target of rapamycin, an immunosuppressant that also blocks vessel restenosis and has potential anticancer applications. mTOR interacts with the raptor and GbetaL proteins to form a complex that is the target of rapamycin. Here, we demonstrate that mTOR is also part of a distinct complex defined by the novel protein rictor (rapamycin-insensitive companion of mTOR). Rictor shares homology with the previously described pianissimo from D. discoidieum, STE20p from S. pombe, and AVO3p from S. cerevisiae. Interestingly, AVO3p is part of a rapamycin-insensitive TOR complex that does not contain the yeast homolog of raptor and signals to the actin cytoskeleton through PKC1. Consistent with this finding, the rictor-containing mTOR complex contains GbetaL but not raptor and it neither regulates the mTOR effector S6K1 nor is it bound by FKBP12-rapamycin. We find that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals.

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Research works printed but not linked: 20

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Metadata

Authors
Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M.
Affiliations
  • Whitehead Institute for Biomedical Research (US)
  • Memorial Sloan Kettering Cancer Center (US)
Corresponding author
Sabatini, David M
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2004-07
Volume
14
Issue
14
Pages
1296-1302
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2004.06.054
OpenAlex
W2065887259
Cited by
2,665
References
1
Citations by year
2026: 43 · 2025: 60 · 2024: 74 · 2023: 103 · 2022: 103 · 2021: 134 · 2020: 120 · 2019: 124 · 2018: 137 · 2017: 121 · 2016: 147 · 2015: 170 · 2014: 160 · 2013: 157 · 2012: 167
FWCI
25.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (P30CA008748)
  • National Institute of Allergy and Infectious Diseases (R01AI047389)
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 › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Keywords
Rictor, mTOR, TOR signaling, raptors, actin cytoskeleton, protein kinase C alpha, S6K1
MeSH terms
Regulatory-Associated Protein of mTOR, Rapamycin-Insensitive Companion of mTOR Protein, Actins, Amino Acid Sequence, Animals, Carrier Proteins, Cytoskeleton, Drosophila, Electrophoresis, Polyacrylamide Gel, Fluorescent Antibody Technique, HeLa Cells, Humans, Molecular Sequence Data, Phosphorylation, Precipitin Tests, Protein Kinase C, Protein Kinases, Proteins, Transfection, Immunoblotting, Sequence Alignment, Conserved Sequence, Sequence Analysis, DNA, DNA Primers, Sirolimus, RNA Interference, RNA, Small Interfering, Gene Components, Adaptor Proteins, Signal Transducing, Protein Kinase C-alpha, TOR Serine-Threonine Kinases

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