IKAP is a scaffold protein of the I kappa B kinase complex.
Cohen, Lucie; Henzel, William J.; Baeuerle, Patrick A.
[Letter] Nature. 395(6699):292-296, September 17, 1998.

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The transcription factor NF-kappa B coordinates the activation of numerous genes in response to pathogens and pro-inflammatory cytokines, and is, therefore, vital in the development of acute and chronic inflammatory diseases [1-6]. NF-kappa B is activated by phosphorylation of its inhibitory subunit, I kappa B-alpha [7], on serine residues 32 and 36 by cytokine-activated I kappa B kinases (IKKs); this phosphorylation precedes rapid degradation of I kappa B [8-11]. IKK-alpha and IKK-beta isozymes are found in large complexes of relative molecular mass 700,000-900,000 (Mr 70K-90K), but little is known about other components that organize and regulate these complexes [12-17]. IKK-alpha was independently discovered as a NF-kappa B-inducing kinase [18] (NIK)-associated protein in a yeast two-hybrid screen [19], and IKK-beta was also identified by homology screening [20]. It is, however, unknown whether NIK is part of the IKK complex. Here we isolate large, interleukin-1-inducible IKK complexes that contain NIK, IKK-alpha, IKK-beta, I kappa B-alpha, NF-kappa B/RelA and a protein of Mr 150K. This latter component is a new protein, termed IKK-complex-associated protein (IKAP), which can bind NIK and IKKs and assemble them into an active kinase complex. We show that IKAP is a scaffold protein and a regulator for three different kinases involved in pro-inflammatory cytokine signalling.

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