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TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme

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Toll-like receptors (TLRs) as well as the receptors for tumor necrosis factor (TNF-R) and interleukin-1 (IL-1R) play an important role in innate immunity by regulating the activity of distinct transcription factors such as nuclear factor-κB (NF-κB). TLR, IL-1R and TNF-R signaling to NF-κB converge on a common IκB kinase complex that phosphorylates the NF-κB inhibitory protein IκBα. However, upstream signaling components are in large part receptor-specific. Nevertheless, the principles of signaling are similar, involving the recruitment of specific adaptor proteins and the activation of kinase cascades in which protein-protein interactions are controlled by poly-ubiquitination. In this review, we will discuss our current knowledge of NF-κB signaling in response to TLR-4, TNF-R and IL-1R stimulation, with a special focus on the similarities and dissimilarities among these pathways.

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Correspondence to R. Beyaert.

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Received 5 February 2008; received after revision 2 April 2008; accepted 25 April 2008

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Verstrepen, L., Bekaert, T., Chau, TL. et al. TLR-4, IL-1R and TNF-R signaling to NF-κB: variations on a common theme. Cell. Mol. Life Sci. 65, 2964–2978 (2008). https://doi.org/10.1007/s00018-008-8064-8

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  • DOI: https://doi.org/10.1007/s00018-008-8064-8

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