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Signal transduction

Docking IκB kinases

Nature volume 395, pages 225–226 (1998)Cite this article

In response to stress or inflammatory and immune reactions, mammalian cells rapidly send a transcription factor called NF-κB into the nucleus. Once there, this protein activates the transcription of specific genes, eliciting various cellular responses. Without the right extracellular signals, however, NF-κB is kept under tight control in the cytoplasm, coupled to inhibitory IκB proteins (IκBα, β and ε), which block its transport into the nucleus. NF-κB is critical for proper immune function, cell growth and survival, and anomalous activation is associated with inflammatory and neoplastic diseases and viral infection.

Several laboratories have established that signal-induced phosphorylation is accomplished by an intriguingly large IKK complex. Two IKKs — IKK-α and IKK-β — have been cloned3,4, and shown to be part of multi-protein complexes in the appropriate size range (relative molecular mass, Mr, 800,000). To date, they are the only kinases known to phosphorylate IκBα at the same residues that are modified in response to agents that activate NF-κB (such as tumour-necrosis factor-α (TNF-α), interleukin-1 (IL-1) and lipopolysaccharide). Moreover, IKK-α and IKK-β are both stimulated by TNF-α or IL-1.

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Figure 1: Putative connections between IκB kinases, scaffold proteins and signalling molecules in the activation of NF-κB.

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  1. the Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13122, Berlin, Germany

    Claus Scheidereit

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  1. Claus Scheidereit
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Scheidereit, C. Docking IκB kinases. Nature 395, 225–226 (1998). https://doi.org/10.1038/26121

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