Positive and Negative Regulation of IκB Kinase Activity Through IKKβ Subunit Phosphorylation

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Science  09 Apr 1999:
Vol. 284, Issue 5412, pp. 309-313
DOI: 10.1126/science.284.5412.309

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IκB [inhibitor of nuclear factor κB (NF-κB)] kinase (IKK) phosphorylates IκB inhibitory proteins, causing their degradation and activation of transcription factor NF-κB, a master activator of inflammatory responses. IKK is composed of three subunits—IKKα and IKKβ, which are highly similar protein kinases, and IKKγ, a regulatory subunit. In mammalian cells, phosphorylation of two sites at the activation loop of IKKβ was essential for activation of IKK by tumor necrosis factor and interleukin-1. Elimination of equivalent sites in IKKα, however, did not interfere with IKK activation. Thus, IKKβ, not IKKα, is the target for proinflammatory stimuli. Once activated, IKKβ autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response.

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