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

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.