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Constitutive Nuclear Expression of the IB Kinase Complex and Its Activation in Human Neutrophils ¹

Pulmonary Division, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada

A singular feature of human neutrophils is that they constitutively express substantial amounts of NF-B/Rel proteins and IB- in the nucleus. In this study, we show that in these cells, IB kinase (IKK), IKK, and IKK also partially localize to the nucleus, whereas IKK-related kinases (IKK, TANK-binding kinase-1) are strictly cytoplasmic, and the NF-B-inducing kinase is strictly nuclear. Following neutrophil activation, IKK and IKK become transiently phosphorylated in both the cytoplasm and nucleus, whereas IKK transiently vanishes from both compartments in what appears to be an IKK-dependent process. These responses are paralleled by the degradation of IB-, and by the phosphorylation of RelA on serine 536, in both compartments. Although both proteins can be IKK substrates, inhibition of IKK prevented IB- phosphorylation, while that of RelA was mostly unaffected. Finally, we provide evidence that the nuclear IKK isoforms (, , ) associate with chromatin following neutrophil activation, which suggests a potential role in gene regulation. This is the first study to document IKK activation and the phosphorylation of NF-B/Rel proteins in primary neutrophils. More importantly, our findings unveil a hitherto unsuspected mode of activation for the IKK/IB signaling cascade within the cell nucleus.

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The JI 2005 175: 1359-1360. [Full Text]  

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