Nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor and an essential mediator of gene expression during activation of immune and inflammatory responses. NF-κB mediates the expression of a great variety of genes in response to extracellular stimuli. NF-κB is associated with IκB proteins in the cell cytoplasm, which inhibit NF-κB activity. Phosphorylation of I-kappaB by IκB kinase (IKK) complex leads to degradation of I-kappaB and activation of NF-κB. The IKK complex contains IKKα, IKKβ, and IKKγ. A novel IKK related kinase was recently identified and designated TBK1 (TANK-binding kinase 1), NAK (NF-κB-activating kinase), and T2K. NAK/TBK1 activates IKKβ through direct phosphorylation. NAK/TBK1 is activated by growth factors and PMA and mediates IKK and NF-κB 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.
