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Background
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Nuclear factor kappa B (NF-?oB) is a ubiquitous transcription factor and an essential mediator of gene expression during activation of immune and inflammatory responses. NF-?oB mediates the expression of a great variety of genes in response to extracellular stimuli including IL-1, TNF?±, and bacteria product LPS. NF-?oB is associated with I?oB proteins in the cell cytoplasm, which inhibit NF-?oB activity. I?oB kinase (IKK), which phosphorylates I?oB and mediates I?oB degradation and NF-?oB activation, was recently identified by several laboratories. IKK is a serine protein kinase, and the IKK complex contains alpha and beta subunits (IKK?±, and IKK?2,). IKK?±, and IKK?2, interact with each other and both are essential for the NF-?oB activation. IKK?±, specifically phosphorylates I?oB-?±, while IKK?2, phosphorylates both I?oB-?±, and I?oB-?2,. Another molecule in the IKK complex termed IKK?3 (also known as NEMO) interacts with IKK?2, and is required for the activation of IKK complex and NF-?oB by LPS, PMA, TNF, and IL-1 stimulation. IKK?3 was also shown to bind to RIP and NIK and to mediate TNF-induced NF-?oB activation. IKK?μ is required for the activation of NF-?oB by PMA and T cell receptors but not by TNF?±, and IL-1. IKK?μ message is expressed in a variety of tissues and is inducible by TNF?±, IL-1, and LPS.
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