Journal
FASEB JOURNAL
Volume 24, Issue 9, Pages 3490-3499Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.09-151290
Keywords
apoptosis; cell survival; serine/threonine kinases; tumor promoter
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Funding
- Hormel Foundation
- U.S. National Institutes of Health [CA077646, CA111536, CA120388, R37CA081064, ES016548]
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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 I kappa B alpha at Ser-32, leading to I kappa B alpha degradation. The phosphorylation of I kappa B alpha promotes the activation and translocation of the nuclear factor-kappa B (NF-kappa B) subunits p65 and p50 to the nucleus. The net result is an increased NF-kappa B activity, which serves as a mechanism for RSK2 blockade of TNF-alpha-induced apoptosis and enhanced cell survival.-Peng, C., Cho, Y.-Y., Zhu, F., Xu, Y.-M., Wen, W., Ma, W.-Y., Bode, A. M., Dong, Z. RSK2 mediates NF-kappa B activity through the phosphorylation of I kappa B alpha in the TNF-R1 pathway. FASEB J. 24, 3490-3499 (2010). www.fasebj.org
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