IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation

F Mercurio, H Zhu, BW Murray, A Shevchenko… - Science, 1997 - science.org
F Mercurio, H Zhu, BW Murray, A Shevchenko, BL Bennett, J Li, DB Young, M Barbosa…
Science, 1997science.org
Activation of the transcription factor nuclear factor kappa B (NF-κB) is controlled by
sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IκB. A
large multiprotein complex, the IκB kinase (IKK) signalsome, was purified from HeLa cells
and found to contain a cytokine-inducible IκB kinase activity that phosphorylates IκB-α and
IκB-β. 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 …
Activation of the transcription factor nuclear factor kappa B (NF-κB) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IκB. A large multiprotein complex, the IκB kinase (IKK) signalsome, was purified from HeLa cells and found to contain a cytokine-inducible IκB kinase activity that phosphorylates IκB-α and IκB-β. 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-κB–dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-κB signaling pathway.
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