Pro-inflammatory cytokines activate the transcription factor NF-kappa B by stimulating the activity of a protein kinase that phosphorylates Ikappa B, an inhibitor of NF-kappa B, at sites that trigger its ubiquitination and degradation. A large, cytokine-responsive Ikappa B kinase (IKK) complex has been purified and the genes encoding 2 of its subunits have been cloned. These subunits, IKK-alpha and Ikk-beta, are protein kinases whose function is needed for NF-kappa B activation by pro-inflammatory stimuli. IKK is composed of similar amounts of IKK-alpha, Ikk-beta, which are differentially processed forms of a third subunit, IKK-gamma. Ikk-gamma interacts preferentially with IKK-beta and is required for the activation of the IKK complex.