How NF-κB is activated:: the role of the IκB kinase (IKK) complex

Rel/NF-kappa B transcription factors are primarily regulated by association with inhibitor I kappa B proteins. Thus, in most cells NF-kappa B exists in the cytoplasm in an inactive complex bound to I kappa B. Most agents that activate NF-kappa B do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of I kappa B. The key regulatory step in this pathway involves activation of a high molecular weight I kappa B kinase (IKK) complex, whose catalysis is generally carried out by a heterodimeric kinase consisting of IKK alpha and IKK beta subunits. This review describes the identification of proteins in the IKK complex, and the regulation and physiological functions of IKK.