Abstract
The ribosomal S6 kinase 2 (RSK2) is a well-known serine/threonine kinase and a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins. It is activated downstream of the MEK/ERKs cascade by mitogenic stimuli such as EGF or TPA. Here, we show that RSK2 is activated by treatment with tumor necrosis factor-alpha (TNF-alpha) and directly phosphorylates IkappaBalpha at Ser-32, leading to IkappaBalpha degradation. The phosphorylation of IkappaBalpha promotes the activation and translocation of the nuclear factor-kappaB (NF-kappaB) subunits p65 and p50 to the nucleus. The net result is an increased NF-kappaB activity, which serves as a mechanism for RSK2 blockade of TNF-alpha-induced apoptosis and enhanced cell survival.
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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Animals
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Caspase 3 / metabolism
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Caspase 8 / metabolism
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Cell Line
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Cell Line, Tumor
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Electrophoretic Mobility Shift Assay
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HeLa Cells
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Humans
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I-kappa B Proteins / metabolism*
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Immunoblotting
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Immunoprecipitation
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Mice
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NF-KappaB Inhibitor alpha
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NF-kappa B / metabolism*
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NF-kappa B p50 Subunit / metabolism
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Phosphorylation / drug effects
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Protein Binding
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Protein Transport / drug effects
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Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
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Transcription Factor RelA / metabolism
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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I-kappa B Proteins
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NF-kappa B
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NF-kappa B p50 Subunit
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NFKBIA protein, human
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Nfkbia protein, mouse
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Transcription Factor RelA
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Tumor Necrosis Factor-alpha
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NF-KappaB Inhibitor alpha
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Ribosomal Protein S6 Kinases, 90-kDa
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ribosomal protein S6 kinase, 90kDa, polypeptide 3
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Caspase 3
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Caspase 8