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IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation

SciencePublished 31 October 1997
Frank Mercurio, Hengyi Zhu, Brion W. Murray, Andrej Shevchenko, Brydon L. Bennett, Jian Wu Li
Citations2,043
SJR quartileQ1
SJR score10.42
SNIP6.62

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.

Keywords

Immunology and MicrobiologyBiochemistry, Genetics and Molecular Biology