Cited by 275PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer
Rac1 Regulates the Activity of mTORC1 and mTORC2 and Controls Cellular Size
Open accessSaci, Abdelhafid, Cantley, Lewis C., Carpenter, Christopher L.·2011·Molecular Cell
Abstract
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two separate complexes, mTORC1 and mTORC2, that function to control cell size and growth in response to growth factors, nutrients, and cellular energy levels. Low molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 complex, but regulation of mTORC2 is poorly understood. Here, we report that Rac1, a member of the Rho family of GTPases, is a critical regulator of both mTORC1 and mTORC2 in response to growth-factor stimulation. Deletion of Rac1 in primary cells using an inducible-Cre/Lox approach inhibits basal and growth-factor activation of both mTORC1 and mTORC2. Rac1 appears to bind directly to mTOR and to mediate mTORC1 and mTORC2 localization at specific membranes. Binding of Rac1 to mTOR does not depend on the GTP-bound state of Rac1, but on the integrity of its C-terminal domain. This function of Rac1 provides a means to regulate mTORC1 and mTORC2 simultaneously.
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Crossref · 10.1016/j.molcel.2011.03.017
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Rac1 appears to activate mTOR and its downstream target p70S6K.
“First, Rac1 appears to activate mTOR and its downstream target p70S6K (70-kDa ribosomal S6 kinase) 57, 58, a kinase essential for switching on translation initiation 48, 49.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [58]
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References 49 · Cited by 275
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- Authors
- Saci, A., Cantley, L. C., & Carpenter, C. L.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Saci, Abdelhafid
- Cantley, Lewis C.
- ORCID
- Cantley, Lewis C.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 42
- Issue
- 1
- Pages
- 50-61
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3750737
- OpenAlex
- W2059019158
- Cited by
- 275
- References
- 49
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 16 · 2023: 16 · 2022: 15 · 2021: 11 · 2020: 23 · 2019: 18 · 2018: 23 · 2017: 21 · 2016: 15 · 2015: 14 · 2014: 16 · 2013: 18 · 2012: 40
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1r01ca113559-01a1)
- National Cancer Institute (R01 CA113559, 5R01 CA113559, P01CA120964)
- National Institute of General Medical Sciences (R01GM056203, R01-GM41890, R01GM041890)
- 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 › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- Rac1, mTORC1, mTORC2, mTOR, Rho GTPases, cell size control, growth factor signaling, cell growth
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Mechanistic Target of Rapamycin Complex 2, Animals, Cells, Cultured, Guanosine Diphosphate, Guanosine Triphosphate, Humans, Neuropeptides, Protein Binding, Proteins, Subcellular Fractions, Signal Transduction, Mice, Knockout, Phosphatidylinositol 3-Kinases, rac GTP-Binding Proteins, rac1 GTP-Binding Protein, RNA, Small Interfering, Multiprotein Complexes, Cell Size, Proto-Oncogene Proteins c-akt, Mice, TOR Serine-Threonine Kinases
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