MoBio Signaling by NF-kB Chapter 6

NF-κB can be activated by a variety of stimuli, including TNF-α (tumor necrosis factor α), interleukin 1 (IL-1), T and B cell mitogens, bacterial lipopolysaccharide (LPS) and viral proteins. The following figure shows the TNF-α 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-κB-inducing kinase).

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Figure 6-F-2. Activation of NF-κB by the TNF-α 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 IκB kinase (IKK).
(3) The active IKK activates NF-κB by degrading the inhibitor protein IκB (see Regulation of NF-κB in Chapter 4).
(4) After NF-κB is activated, it may serve as a transcription factor or inhibit apoptosis.