The transcription factor NF?B is retained in the cytoplasm in an inactive form by the inhibitory protein I?B. Activation of NF?B requires that I?B be phosphorylate on specific serine residues, which results in targeted degradation of I?B. I?B kinase ? (IKK?), previously designated CHUK, interacts with I?B-? and specifically phosphorylates I?B-? on Serines 32 and 36, the sites that trigger its degradation. IKK? appears to be critical for NF?B activation in response to proinflammatory cytokines. Phosphorylation of I?B by IKK? is stimulated by the NF?B inducing kinase (NIK), which itself is a central regulato for NF?B activation in response to TNF and IL-1. The functional IKK complex contains three subunits, IKK?, IKK? and IKK? (also designated NEMO), and each appear to make essential contributions to I?B phosphorylation.