Abstract
IkappaB [inhibitor of nuclear factor kappaB (NF-kappaB)] kinase (IKK) phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses. IKK is composed of three subunits-IKKalpha and IKKbeta, which are highly similar protein kinases, and IKKgamma, a regulatory subunit. In mammalian cells, phosphorylation of two sites at the activation loop of IKKbeta was essential for activation of IKK by tumor necrosis factor and interleukin-1. Elimination of equivalent sites in IKKalpha, however, did not interfere with IKK activation. Thus, IKKbeta, not IKKalpha, is the target for proinflammatory stimuli. Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Cell Line
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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HeLa Cells
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Helix-Loop-Helix Motifs
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Humans
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I-kappa B Kinase
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I-kappa B Proteins
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Interleukin-1 / pharmacology
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Leucine Zippers
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MAP Kinase Kinase Kinase 1*
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Molecular Sequence Data
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Mutation
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NF-kappaB-Inducing Kinase
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Phosphorylation
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Phosphoserine / metabolism
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Transfection
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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DNA-Binding Proteins
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I-kappa B Proteins
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Interleukin-1
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Tumor Necrosis Factor-alpha
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Phosphoserine
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Protein Serine-Threonine Kinases
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CHUK protein, human
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human
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MAP Kinase Kinase Kinase 1
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MAP3K1 protein, human