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- Title
Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation.
- Authors
Delhase, M; Hayakawa, M; Chen, Y; Karin, M
- Abstract
IkappaB [inhibitor of nuclear factor kappaB (NF-kappaB)] kinase (IKK) phosphorylates IkappaB inhibitory proteins, causing their degradation and activation of transcription factor NF-kappaB, a master activator of inflammatory responses. IKK is composed of three subunits-IKKalpha and IKKbeta, which are highly similar protein kinases, and IKKgamma, a regulatory subunit. In mammalian cells, phosphorylation of two sites at the activation loop of IKKbeta was essential for activation of IKK by tumor necrosis factor and interleukin-1. Elimination of equivalent sites in IKKalpha, however, did not interfere with IKK activation. Thus, IKKbeta, not IKKalpha, is the target for proinflammatory stimuli. Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response.
- Publication
Science (New York, N.Y.), 1999, Vol 284, Issue 5412, p309
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.284.5412.309