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

Cong Peng1, Yong-Yeon Cho, Feng Zhu

  • 1The Hormel Institute, University of Minnesota, 801 16th Ave N.E., Austin, MN 55912, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|April 14, 2010
PubMed

Insights

Ribosomal S6 kinase 2 (RSK2) activation by tumor necrosis factor-alpha (TNF-alpha) leads to increased nuclear factor-kappaB (NF-kappaB) activity. This RSK2-mediated pathway promotes cell survival by blocking TNF-alpha-induced apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Immunology

Background:

  • Ribosomal S6 kinase 2 (RSK2) is a p90 ribosomal S6 kinase (p90RSK) family member.
  • RSK2 is activated by mitogenic stimuli via the MEK/ERKs pathway.
  • Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory cytokine.

Purpose of the Study:

  • To investigate the role of RSK2 in TNF-alpha signaling.
  • To determine if RSK2 phosphorylates IkappaBalpha.
  • To elucidate the mechanism by which RSK2 influences TNF-alpha-induced apoptosis.

Main Methods:

  • Cell treatment with TNF-alpha.
  • Western blotting to detect protein phosphorylation and degradation.
  • Analysis of nuclear factor-kappaB (NF-kappaB) activation and translocation.

Main Results:

  • RSK2 is activated by TNF-alpha treatment.
  • RSK2 directly phosphorylates IkappaBalpha at Ser-32, causing its degradation.
  • RSK2 activation leads to increased nuclear translocation and activity of NF-kappaB subunits p65 and p50.

Conclusions:

  • RSK2 activation by TNF-alpha enhances NF-kappaB activity.
  • RSK2-mediated NF-kappaB activation blocks TNF-alpha-induced apoptosis.
  • RSK2 plays a critical role in promoting cell survival under TNF-alpha stimulation.

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