| Background |
The NF-κB/Rel transcription factors are present in the cytosol in an inactive state, complexed with the inhibitory IκB proteins Most agents that activate NF-κB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IκB The key regulatory step in this pathway involves activation of a high molecular weight IκB kinase (IKK) complex whose catalysis is generally carried out by three tightly associated IKK subunits. IKKα and IKKβ serve as the catalytic subunits of the kinase and IKKγ serves as the regulatory subunit Activation of IKK depends upon phosphorylation at Ser177 and Ser181 in the activation loop of IKKβ (Ser176 and Ser180 in IKKα), which causes conformational changes, resulting in kinase activation.Recently, two homologs of IKKα and IKKβ have been described, called IKKε (also known as IKK-i) and TBK1 (also known as T2K or NAK). Activation of either of these kinases results in NF-κB activation. IKKε contains the kinase domain in its amino terminus, which shares 30% identity to that of IKKα or IKKβ. IKKε is expressed mainly in immune cells and may play a special role in the immune response.
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