Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton
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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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mTORC2 modulates cell morphology via PKCα signaling.
“It was initially shown that mTORC2 modulates cell morphology via PKCα signaling [43].”
From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [43]
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- 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
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 14
- Issue
- 14
- Pages
- 1296-1302
- ISSN
- 0960-9822 (ISSN-L)
- 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
- bronze
- doi.org
- 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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