The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex
Abstract
Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of cancer and diabetes. Akt/PKB activation requires the phosphorylation of Thr 308 in the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser 473 within the carboxyl-terminal hydrophobic motif by an unknown kinase. We show that in Drosophila and human cells the target of rapamycin (TOR) kinase and its associated protein rictor are necessary for Ser 473 phosphorylation and that a reduction in rictor or mammalian TOR (mTOR) expression inhibited an Akt/PKB effector. The rictor-mTOR complex directly phosphorylated Akt/PKB on Ser 473 in vitro and facilitated Thr 308 phosphorylation by PDK1. Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation.
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“Akt is also phosphorylated within the carboxyl-terminal hydrophobic motif at Ser473 by the serine/threonine kinase mammalian target of rapamycin complex 2 (mTORC2), within a rapamycin-insensitive protein complex (27).”
From Mislocalization of the Cell Polarity Protein Scribble Promotes Mammary Tumorigenesis and Is Associated with Basal Breast Cancer (2014) · cites this paper as [27]
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Cites
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Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action
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RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1
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Research works printed but not linked: 1
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Cited by
Sorted by citations
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509
Self-citationmTOR Signaling in Growth, Metabolism, and Disease
Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555
Self-citationTOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
Self-citationAKT/PKB Signaling: Navigating the Network
Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
Metadata
- Authors
- Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Guertin, David A.
- Ali, Siraj M.
- Sabatini, David M.
- Venue
- Science
- Published
- 2005-02-18
- Volume
- 307
- Issue
- 5712
- Pages
- 1098-1101
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4238567307
- Cited by
- 6,216
- References
- 28
- Citations by year
- 2026: 119 · 2025: 176 · 2024: 229 · 2023: 275 · 2022: 254 · 2021: 323 · 2020: 324 · 2019: 318 · 2018: 350 · 2017: 329 · 2016: 303 · 2015: 396 · 2014: 358 · 2013: 386 · 2012: 378
- FWCI
- 86.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01 AI47389, 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 › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Akt/protein kinase B, Rictor, mTOR, TOR signaling, Ser473 phosphorylation, PDPK1, kinase regulation, PTEN, cancer, therapeutic target, Drosophila
- MeSH terms
- Regulatory-Associated Protein of mTOR, Rapamycin-Insensitive Companion of mTOR Protein, Animals, Carrier Proteins, Cell Line, Drosophila melanogaster, Enzyme Activation, Humans, Phosphorylation, Protein Kinases, Proteins, Proto-Oncogene Proteins, Serine, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Drosophila Proteins, RNA Interference, Cell Line, Tumor, Immunoprecipitation, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Hydrophobic and Hydrophilic Interactions, TOR Serine-Threonine Kinases, 3-Phosphoinositide-Dependent Protein Kinases
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