The mTOR‐regulated phosphoproteome reveals a mechanism of mTORC1‐mediated inhibition of growth factor signaling
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A search for substrates of a growth-promoting kinase revealed a regulatory feedback loop involved in tumor suppression.
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Several factors inhibit insulin signaling including oxidative stress, which occurs in DS due to the triplication of the SOD1 and APP genes on Hsa21, and mTORC1-mediated phosphorylation of the IRS-1 protein.
“Several factors inhibit insulin signaling including oxidative stress, which occurs in DS due to the triplication of the SOD1 and APP genes on Hsa21, 68 and mTORC1‐mediated phosphorylation of the IRS‐1 protein 69 .”
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- Authors
- Hsu, P. P., Kang, S. A., Rameseder, J., Zhang, Y., Ottina, K. A., Lim, D., Peterson, T. R., Choi, Y., Gray, N. S., Yaffe, M. B., Marto, J. A., & Sabatini, D. M.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Dana-Farber Cancer Institute (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Corresponding author
- Sabatini, David M.
- ORCID
- Venue
- Science
- Published
- 2011-06-10
- Volume
- 332
- Issue
- 6035
- Pages
- 1317-1322
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3177140
- OpenAlex
- W2111352469
- Cited by
- 1,084
- References
- 2
- Citations by year
- 2026: 26 · 2025: 27 · 2024: 49 · 2023: 50 · 2022: 51 · 2021: 60 · 2020: 93 · 2019: 56 · 2018: 72 · 2017: 82 · 2016: 86 · 2015: 88 · 2014: 104 · 2013: 102 · 2012: 108
- FWCI
- 44.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PubMed Central
- Funders
- U.S. Department of Defense (W81XWH-07-0448, W81XWH)
- Howard Hughes Medical Institute
- W. M. Keck Foundation
- National Institutes of Health (5p50gm068762-10, W81XWH, AI47389, CA112967, GM68762)
- National Cancer Institute (CA 112967, U54CA112967, CA103866, R01CA103866, R01CA129105)
- National Institute of General Medical Sciences (GM 68762, T32GM007753, P50-GM068762)
- National Institute of Allergy and Infectious Diseases (R37AI047389, AI47389), R01AI047389)
- National Institute of Environmental Health Sciences (R01ES015339, ES-015339)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- mTOR, mTORC1, mTORC2, phosphoproteome, substrate specificity, sequence motifs, insulin signaling, Grb10, phosphatidylinositol 3-kinase, tuberous sclerosis complex 2, growth factor signaling, protein phosphorylation
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Animals, Cell Line, Humans, Insulin, Naphthyridines, Phosphoproteins, Phosphorylation, Proteins, Mass Spectrometry, Signal Transduction, Sirolimus, Proteome, Intercellular Signaling Peptides and Proteins, Multiprotein Complexes, Mice, GRB10 Adaptor Protein, TOR Serine-Threonine Kinases
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