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

• DOI: 10.1093/intimm/11.8.1357
• Publication Date: 2002-07-26T18:35:13Z
• Authors: Takahiro Shimada; Taro Kawai; Kiyoshi Takeda; Makoto Matsumoto; Jun-ichiro Inoue; Yoichi Tatsumi; Akihisa Kanamaru; Shizuo Akira
• Keywords: Inflammation; Lipopolysaccharides; Transcriptional Activation; 0301 basic medicine; Macrophages; Molecular Sequence Data; NF-kappa B; Sequence Analysis, DNA; Macrophage Activation; Protein Serine-Threonine Kinases; I-kappa B Kinase; DNA-Binding Proteins; Mice; 03 medical and health sciences; NF-KappaB Inhibitor alpha; Enzyme Induction; Animals; Cytokines; Humans; I-kappa B Proteins; Amino Acid Sequence; Phosphorylation

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-alpha or IKK-beta. The C-terminal portion contains a leucine zipper and a potential helix-loop-helix domain, as in the case of IKK-alpha and IKK-beta. IKK-i is expressed mainly in immune cells, and is induced in response to proinflammatory cytokines such as tumor necrosis factor-alpha, IL-1 and IL-6, in addition to LPS. Overexpression of wild-type IKK-i phosphorylated serine residues Ser32 and Ser36 of IkappaB-alpha (preferentially Ser36), and significantly stimulated NF-kappaB activation. These results suggest that IKK-i is an inducible IkappaB kinase which may play a special role in the immune response.