Abstract
The raptor-mTOR protein complex is a key component of a nutrient-sensitive signaling pathway that regulates cell size by controlling the accumulation of cellular mass. How nutrients regulate signaling through the raptor-mTOR complex is not well known. Here we show that a redox-sensitive mechanism regulates the phosphorylation of the raptor-mTOR effector S6K1, the interaction between raptor and mTOR, and the kinase activity of the raptor-mTOR complex. In cells treated with the oxidizing agents diamide or phenylarsine oxide, S6K1 phosphorylation increased and became insensitive to nutrient deprivation. Conversely, the reducing reagent BAL (British anti-Lewisite, also known as 2,3-dimercapto-1-propanol) inhibits S6K1 phosphorylation and stabilizes the interaction of mTOR and raptor to mimic the state of the complex under nutrient-deprived conditions. Our findings suggest that a redox-based signaling mechanism may participate in regulating the nutrient-sensitive raptor-mTOR complex and pathway.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Arsenicals / pharmacology
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Cell Line
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Diamide / pharmacology
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Dimercaprol / pharmacology
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Humans
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Multiprotein Complexes
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Oxidants / pharmacology
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Oxidation-Reduction
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Phosphorylation
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Protein Kinases / chemistry
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Protein Kinases / genetics
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Protein Kinases / metabolism*
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Proteins / chemistry
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Proteins / genetics
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Proteins / metabolism*
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RNA, Small Interfering / genetics
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Regulatory-Associated Protein of mTOR
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Ribosomal Protein S6 Kinases, 70-kDa / metabolism
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Signal Transduction / drug effects
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TOR Serine-Threonine Kinases
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Arsenicals
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Multiprotein Complexes
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Oxidants
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Proteins
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RNA, Small Interfering
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RPTOR protein, human
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Recombinant Proteins
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Regulatory-Associated Protein of mTOR
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Dimercaprol
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oxophenylarsine
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Diamide
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Protein Kinases
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MTOR protein, human
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Ribosomal Protein S6 Kinases, 70-kDa
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TOR Serine-Threonine Kinases
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ribosomal protein S6 kinase, 70kD, polypeptide 1