NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176
| Autor: | L, Ling, Z, Cao, D V, Goeddel |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Binding Sites
cells Molecular Sequence Data Protein Serine-Threonine Kinases Biological Sciences environment and public health I-kappa B Kinase Enzyme Activation enzymes and coenzymes (carbohydrates) Mutation Serine Animals Humans Amino Acid Sequence biological phenomena cell phenomena and immunity Phosphorylation skin and connective tissue diseases Sequence Alignment HeLa Cells Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 95(7) |
| ISSN: | 0027-8424 |
| Popis: | Activation of the transcription factor NF-kappaB by inflammatory cytokines involves the successive action of NF-kappaB-inducing kinase (NIK) and two IkappaB kinases, IKK-alpha and IKK-beta. Here we show that NIK preferentially phosphorylates IKK-alpha over IKK-beta, leading to the activation of IKK-alpha kinase activity. This phosphorylation of IKK-alpha occurs specifically on Ser-176 in the activation loop between kinase subdomains VII and VIII. A mutant form of IKK-alpha containing alanine at residue 176 cannot be phosphorylated or activated by NIK and acts as a dominant negative inhibitor of interleukin 1- and tumor necrosis factor-induced NF-kappaB activation. Conversely, a mutant form of IKK-alpha containing glutamic acid at residue 176 is constitutively active. Thus, the phosphorylation of IKK-alpha on Ser-176 by NIK may be required for cytokine-mediated NF-kappaB activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|