IKK-i, a novel lipopolysaccharide-inducible kinase that is related to IκB kinases

Using the suppression subtractive hybridization technique, we isolated a novel kinase, IKK-i, whose message is drastically induced by lipopolysaccharide (LPS) in the mouse macrophage cell line RAW264.7. The predicted protein contains the kinase domain in its N-terminus, which shares 30% identity to that of IKK-α or IKK-β. The C-terminal portion contains a leucine zipper and a potential helix-loop-helix domain, as in the case of IKK-α and IKK-β. IKK-i is expressed mainly in immune cells, and is induced in response to proinflammatory cytokines such as tumor necrosis factor-α, IL-1 and IL-6, in addition to LPS. Overexpression of wild-type IKK-i phosphorylated serine residues Ser32 and Ser36 of IκB-α (preferentially Ser36), and significantly stimulated NF-κB activation. These results suggest that IKK-i is an inducible IκB kinase which may play a special role in the immune response.