title: IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK.
abstract: Activation of the transcription factor nuclear factor kappa B (NF-kappaB) by inflammatory cytokines requires the successive action of NF-kappaB-inducing kinase (NIK) and IkappaB kinase-alpha (IKK-alpha). A widely expressed protein kinase was identified that is 52 percent identical to IKK-alpha. IkappaB kinase-beta (IKK-beta) activated NF-kappaB when overexpressed and phosphorylated serine residues 32 and 36 of IkappaB-alpha and serines 19 and 23 of IkappaB-beta. The activity of IKK-beta was stimulated by tumor necrosis factor and interleukin-1 treatment. IKK-alpha and IKK-beta formed heterodimers that interacted with NIK. Overexpression of a catalytically inactive form of IKK-beta blocked cytokine-induced NF-kappaB activation. Thus, an active IkappaB kinase complex may require three distinct protein kinases.
authors.affiliation: Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Woronicz
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: Z
authors.initials: Z
authors.lastname: Cao
authors.forename: M
authors.initials: M
authors.lastname: Rothe
authors.forename: D V
authors.initials: DV
authors.lastname: Goeddel
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D016207:Cytokines; D051550:I-kappa B Kinase; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C496559:CHUK protein, human; C496560:IKBKB protein, human; C496565:IKBKE protein, human