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TBK1 serine/threonine kinase is a member of the IKK family and is involved in NF-kappa B activation and IRF3 signaling. TBK1 is a ubiquitous transcription factor and an essential mediator of gene expression during activation of immune and inflammatory responses. NF-KB mediates the expression of a great variety of genes in response to extracellular stimuli. NF-KB is associated with IKB proteins in the cell cytoplasm, which inhibit NF-KB activity. Phosphorylation of I-KB by IKB kinase (IKK) complex leads to degradation of I-KB and activation of NF-KB. The IKK complex contains IKKa, IKK beta, and IKKK. A novel IKK related kinase was recently identified and designated TBK1 (TANK-binding kinase 1), NAK (NF-KB-activating kinase), and T2K. NAK/TBK1 activates IKK beta through direct phosphorylation. NAK/TBK1 is activated by growth factors and PMA and mediates IKK and NF-kB activation in response to growth factors. NAK/TBK1 functions upstream of NIK and the IKK complex. NAK/TBK1 is also critical in protecting embryonic liver from apoptosis.
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