RSK2 mediates NF-{kappa}B activity through the phosphorylation of IkappaBalpha in the TNF-R1 pathway.
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.
Peng
Cong
C
The Hormel Institute, University of Minnesota, 801 16th Ave N.E., Austin, MN 55912, USA.
Cho
Yong-Yeon
YY
Zhu
Feng
F
Xu
Yan-Ming
YM
Wen
Weihong
W
Ma
Wei-Ya
WY
Bode
Ann M
AM
Dong
Zigang
Z
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D053148:Caspase 3; D053181:Caspase 8
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