Docking IκB kinases (original) (raw)

Signal transduction

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, _M_r, 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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