Activation of NF?B requires that I?B be phosphorylated 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 the sites that trigger its degradation Serines 32 and 36. 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 regulator for NF?B activation in response to TNF and IL-1. The functional IKK complex contains three subunits, IKK?, IKK? and IKK? , and each appear to make essential contributions to I?B phosphorylation.