title: IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation.
abstract: Activation of the transcription factor nuclear factor kappa B (NF-kappaB) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IkappaB. A large multiprotein complex, the IkappaB kinase (IKK) signalsome, was purified from HeLa cells and found to contain a cytokine-inducible IkappaB kinase activity that phosphorylates IkappaB-alpha and IkappaB-beta. Two components of the IKK signalsome, IKK-1 and IKK-2, were identified as closely related protein serine kinases containing leucine zipper and helix-loop-helix protein interaction motifs. Mutant versions of IKK-2 had pronounced effects on RelA nuclear translocation and NF-kappaB-dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-kappaB signaling pathway.
authors.affiliation: Signal Pharmaceuticals, Inc., 5555 Oberlin Drive, San Diego, CA 92121, USA. fmercuri@signalpharm.com
authors.forename: F
authors.initials: F
authors.lastname: Mercurio
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.forename: B W
authors.initials: BW
authors.lastname: Murray
authors.forename: A
authors.initials: A
authors.lastname: Shevchenko
authors.forename: B L
authors.initials: BL
authors.lastname: Bennett
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: D B
authors.initials: DB
authors.lastname: Young
authors.forename: M
authors.initials: M
authors.lastname: Barbosa
authors.forename: M
authors.initials: M
authors.lastname: Mann
authors.forename: A
authors.initials: A
authors.lastname: Manning
authors.forename: A
authors.initials: A
authors.lastname: Rao
mesh_terms: D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation; D006367:HeLa Cells; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051550:I-kappa B Kinase; D017874:Immediate-Early Proteins / Q000378:metabolism; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases