IKK-1 AND IKK-2 - CYTOKINE-ACTIVATED I-KAPPA-B KINASES ESSENTIAL FOR NF-KAPPA-B ACTIVATION

Activation of the transcription factor nuclear factor kappa B (NF-kapp a B) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit I kappa B. A large multiprotein complex, the I kappa B kinase (IKK) signalsome, was purified from Hela cells and found to contain a cytokine-inducible I kappa B kinase acti vity that phosphorylates I kappa B-alpha and I kappa B-beta. Two compo nents of the IKK signalsome, IKK-1 and IKK-2, were identified as close ly related protein serine kinases containing leucine zipper and helix- loop-helix protein interaction motifs. Mutant versions of IKK-2 had pr onounced effects on RelA nuclear translocation and NF-kappa B-dependen t reporter activity, consistent with a critical role for the IKK kinas es in the NF-kappa B signaling pathway.