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    Science. 1997 Oct 31;278(5339):860-6.

    IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation.

    Mercurio F, Zhu H, Murray BW, Shevchenko A, Bennett BL, Li J, Young DB, Barbosa M, Mann M, Manning A, Rao A.

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    Signal Pharmaceuticals, Inc., 5555 Oberlin Drive, San Diego, CA 92121, USA. fmercuri@signalpharm.com

    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.

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    PMID:
    9346484
    [PubMed - indexed for MEDLINE]

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