NFKB Signaling Pathway

NF-κB Signaling Pathway. A cartoon representing the cascade of biochemical events that are initiated by various stimuli, eventually leading to NF-κB nuclear translocation and transcriptional activation. Recruitment of different adaptor molecules to different receptor complexes coupled with activation of different downstream kinases is shown. There are mainly two signaling pathways leading to NF-κB activation, classical (also known as canonical) and alternative. The formation and activation of the IKK complex, which consists of catalytically active kinases (e.g., IKKα, IKKβ, and IKKγ) and noncatalytic regulatory proteins (e.g., NEMO and ELKS), is a universal event in both signaling pathways. In the classical signaling pathway, ligand binding to a cell surface receptor leads to the recruitment of adaptor proteins (e.g., TRAF6) to the receptor, leading to the recruitment of IKK complex and subsequent phosphorylation and degradation of the IκB proteins. Unlike the classical signaling pathway, the alternative signaling pathway, which is normally triggered by non-proinflammatory cytokines (e.g., LTβ, BAFF, and CD40L) as well as some viruses (e.g., HTLV and EBV), does not allow the recruitment of NEMO. Instead, ligand binding to a cell surface receptor leads to the recruitment of NIK, which in turn phosphorylates and activates IKKα dimers. Typically, the classical signaling pathway leads to the activation of NF-κB dimers consisting of RelA, c-Rel, RelB, and p50, while the alternative signaling pathway leads to the activation of NF-κB dimers consisting primarily of RelB and p52.

Publication

Regulation of IκBα Function and NF-κB Signaling: AEBP1 Is a Novel Proinflammatory Mediator in Macrophages. (2010) Amin Majdalawieh, et al. Mediators Inflamm. 2010;2010:823821. Figure: F2. Homo sapiens

Disease mentions