RSK2 mediates NF‐κB activity through the phosphorylation of IκBα in the TNF‐R1 pathway
- 12 April 2010
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 24 (9), 3490-3499
- https://doi.org/10.1096/fj.09-151290
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.Keywords
Funding Information
- Hormel Foundation
- National Institutes of Health (CA077646, CA111536, CA120388, R37CA081064, ES016548)
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