Ikappa Balpha is a target for the mitogen-activated 90kDa ribosomal S6 kinase
Open Access
- 1 June 1997
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 16 (11) , 3133-3144
- https://doi.org/10.1093/emboj/16.11.3133
Abstract
The activity of transcription factor NFκB is regulated by its subcellular localization. In most cell types, NFκB is sequestered in the cytoplasm due to binding of the inhibitory protein IκBα. Stimulation of cells with a wide variety of agents results in degradation of IκBα, which allows translocation of NFκB to the nucleus. Degradation of IκBα is triggered by phosphorylation of two serine residues, i.e. Ser32 and Ser36, by as yet unknown kinases. Here we report that the mitogen‐activated 90 kDa ribosomal S6 kinase (p90rsk1) is an IκBα kinase. p90rsk1 phosphorylates IκBα at Ser32 and it physically associates with IκBα in vivo . Moreover, when the function of p90rsk1 is impaired by expression of a dominant‐negative mutant, IκBα degradation in response to mitogenic stimuli, e.g. 12‐ O ‐tetradecanoylphorbol 13‐acetate (TPA), is inhibited. Finally, NFκB cannot be activated by TPA in cell lines that have low levels of p90rsk1. We conclude that p90rsk1 is an essential kinase required for phosphorylation and subsequent degradation of IκBα in response to mitogens.Keywords
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