IκB kinase (IKK)

The IκBs form a small family of related proteins with a core consisting of six or more ankyrin repeats, an N-terminal regulatory domain and a C-terminal domain that contains a PEST motif. There is strong biochemical and genetic evidence that the IKK complex, which consists of two catalytic subunits, IKKα and IKKβ, and a regulatory subunit, IKKγ, is the master regulator of NF-κB-mediated innate immune and inflammatory responses. The best-studied and major IκB protein is IκBα.IκB kinase activity is essential for activation of members of the nuclear factor-kB (NF-κB) family of transcription factors, which play a fundamental role in lymphocyte immunoregulation. Increased NF-κB activity as a result of constitutive IKK-mediated phosphorylation of IκBα has been observed in the development of atherosclerosis, asthma, rheumatoid arthritis, inflammatory bowel diseases, and multiple sclerosis.