RSK2 mediates NF-{kappa}B activity through the phosphorylation of IkappaBalpha in the TNF-R1 pathway

FASEB J. 2010 Sep;24(9):3490-9. doi: 10.1096/fj.09-151290. Epub 2010 Apr 12.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Electrophoretic Mobility Shift Assay
  • HeLa Cells
  • Humans
  • I-kappa B Proteins / metabolism*
  • Immunoblotting
  • Immunoprecipitation
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • NF-kappa B p50 Subunit / metabolism
  • Phosphorylation / drug effects
  • Protein Binding
  • Protein Transport / drug effects
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • I-kappa B Proteins
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Ribosomal Protein S6 Kinases, 90-kDa
  • ribosomal protein S6 kinase, 90kDa, polypeptide 3
  • Caspase 3
  • Caspase 8