The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation.
Recently we purified a 900 kDa cytokine-responsive IkappaB kinase complex (IKK) and molecularly cloned one of its subunits, IKKalpha, a serine kinase. We now describe the molecular cloning and characterization of IKKbeta, a second subunit of the IKK complex. IKKbeta is 50% identical to IKKalpha and like it contains a kinase domain, a leucine zipper, and a helix-loop-helix. Although IKKalpha and IKKbeta can undergo homotypic interaction, they also interact with each other and the functional IKK complex contains both subunits. The catalytic activities of both IKKalpha and IKKbeta make essential contributions to IkappaB phosphorylation and NF-kappaB activation. While the interactions between IKKalpha and IKKbeta may be mediated through their leucine zipper motifs, their helix-loop-helix motifs may be involved in interactions with essential regulatory subunits.
Zandi
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Department of Pharmacology, University of California at San Diego, La Jolla 92093-0636, USA.
Rothwarf
D M
DM
Delhase
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M
Hayakawa
M
M
Karin
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M
D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004789:Enzyme Activation; D006367:HeLa Cells; D019077:Helix-Turn-Helix Motifs; D006801:Humans; D051550:I-kappa B Kinase; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA
D016328:NF-kappa B; D051996:Transcription Factor RelA; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human