Interleukin-1 stimulated activation of the COT catalytic subunit through the phosphorylation of Thr290 and Ser62
| Autor: | Mark Peggie, Nick A. Morrice, Philip Cohen, Margaret J. Stafford |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Protein subunit
Molecular Sequence Data Biophysics IκB kinase Biochemistry Mass Spectrometry Phosphoserine Structural Biology Catalytic Domain Proto-Oncogene Proteins Genetics Humans Amino Acid Sequence COT Protein kinase A Molecular Biology biology IKK Chemistry Autophosphorylation Mutagenesis Cell Biology Proinflammatory cytokine MAP Kinase Kinase Kinases Cell biology Enzyme Activation IκBα Phosphothreonine Mitogen-activated protein kinase Mutation biology.protein Phosphorylation MAP kinase Interleukin-1 |
| Zdroj: | FEBS letters. 580(16) |
| ISSN: | 0014-5793 |
| Popis: | The protein kinase COT/Tpl2 is activated by interleukin-1 (IL-1), TNFalpha and lipopolysaccharide, and its activation by these agonists involves the IkappaB kinase beta (IKKbeta) catalysed phosphorylation of the p105 regulatory subunit. Here, we show that COT activation also requires catalytic subunit phosphorylation, since IL-1beta induced a 5-10-fold activation of a COT mutant unable to bind p105. Activation was paralleled by the phosphorylation of Thr290 and Ser62 and unaffected by the IKKbeta inhibitor PS1145 at concentrations which prevented the degradation of IkappaBalpha. Mutagenesis experiments indicated that COT activation is initiated by Thr290 phosphorylation catalysed by an IL-1-stimulated protein kinase distinct from IKKbeta, while Ser62 phosphorylation is an autophosphorylation event required for maximal activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text