Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Cytokines / immunology
-
DNA-Binding Proteins / metabolism
-
Enzyme Induction
-
Humans
-
I-kappa B Kinase
-
I-kappa B Proteins*
-
Inflammation / immunology
-
Lipopolysaccharides / pharmacology*
-
Macrophage Activation
-
Macrophages / enzymology*
-
Macrophages / immunology*
-
Mice
-
Molecular Sequence Data
-
NF-KappaB Inhibitor alpha
-
NF-kappa B / metabolism
-
Phosphorylation
-
Protein Serine-Threonine Kinases / chemistry
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism*
-
Sequence Analysis, DNA
-
Transcriptional Activation
Substances
-
Cytokines
-
DNA-Binding Proteins
-
I-kappa B Proteins
-
Lipopolysaccharides
-
NF-kappa B
-
NFKBIA protein, human
-
Nfkbia protein, mouse
-
NF-KappaB Inhibitor alpha
-
Protein Serine-Threonine Kinases
-
CHUK protein, human
-
Chuk protein, mouse
-
I-kappa B Kinase
-
IKBKB protein, human
-
IKBKE protein, human
-
Ikbkb protein, mouse
-
Ikbke protein, mouse
Associated data
-
GENBANK/AB016589
-
GENBANK/AB016590