Threonine 66 in the death domain of IRAK-1 is critical for interaction with signaling molecules but is not a target site for autophosphorylation
| Autor: | Andreas Pich, Christian Kollewe, Michael U. Martin, Ping Cao, Detlef Neumann, Klaus Resch |
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| Rok vydání: | 2008 |
| Předmět: |
Threonine
Cell signaling Immunology Genetic Vectors Immunoblotting Biology Kidney Fluorescence Resonance Energy Transfer Immunology and Allergy Humans Immunoprecipitation Phosphorylation Cells Cultured Death domain Kinase TOLLIP Autophosphorylation Intracellular Signaling Peptides and Proteins NF-kappa B Kidney metabolism Cell Biology Cell biology Molecular Weight Interleukin-1 Receptor-Associated Kinases Biochemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Myeloid Differentiation Factor 88 Interleukin-2 Signal transduction Signal Transduction |
| Zdroj: | Journal of leukocyte biology. 84(3) |
| ISSN: | 0741-5400 |
| Popis: | Ligand binding in the TLR/IL-1R family results in the transient formation of an intracellular signaling complex, which contains, amongst others, the serine/threonine-specific kinase IL-1R-associated kinase 1 (IRAK-1). Concomitantly, the kinase function of IRAK-1 becomes activated, resulting in massive autophosphorylation and finally in the dissociation of the initially constituted signaling complex. The death domain (DD) of IRAK-1 mediates the interaction with other molecules of the signaling complex, e.g., the adaptor MyD88, the silencer Tollip, and the activator kinase IRAK-4. The conserved threonine at position 66 (T66), located within the DD, is a putative autophosphorylation target site. Here, we provide evidence that T66 critically impacts the secondary structure of the IRAK-1 DD. Thereby, it ensures the transient manner of interactions between IRAK-1 and the other signaling molecules. This essential role, however, is not regulated by phosphorylation of T66 itself. |
| Databáze: | OpenAIRE |
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