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.