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