Signaling by NF-kB

NF-kB can be activated by a variety of stimuli, including TNF-a (tumor necrosis factor a), interleukin 1 (IL-1), T and B cell mitogens, bacterial lipopolysaccharide (LPS) and viral proteins.  The following figure shows the TNF-a pathway where the activation of IKK by TRAF2 is not well understood.  Current experimental results suggest that some protein kinase in the MAPKKK group is involved, such as NIK (NF-kB-inducing kinase).

Figure 6-F-2.  Activation of NF-kB by the TNF-a pathway.
(1) Binding of TNF-a to its receptor recruits TRADD (TNF receptor-associated death domain protein), RIP (receptor-interacting protein) and TRAF2 (TNF receptor-associated factor 2).
(2) TRAF2 activates IkB kinase (IKK).
(3) The active IKK activates NF-kB by degrading the inhibitor protein IkB (see Regulation of NF-kB in Chapter 4).
(4) After NF-kB  is activated, it may serve as a transcription factor or inhibit apoptosis.

Review Articles:

Nuclear Factor-kB Decoys Suppress Endotoxin-Induced Lung Injury - Mol. Pharma., 2005.

A pervasive role of ubiquitin conjugation in activation and termination of IkB kinase pathways - EMBO Report, 2005.

Signaling to NF-kB - Genes and Development, 2004.

NF-kB activation pathways induced by T cell costimulation - FASEB J., 2003.

Bridging the Gap: Composition, Regulation, and Physiological Function of the IkB Kinase Complex - Molecular and Cellular Biology, 1999.

It's Got You Covered: NF-kB in the Epidermis - J. Cell Biology, 2000..