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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Li, Shyun Strelow, Astrid Wesche, Holger Fontana, Elizabeth J. |
| Description | Author Affiliation: Li S ( Tularik, Inc., 2 Corporate Drive, South San Francisco, CA 94080, USA.); |
| Abstract | Toll/IL-1 receptor family members are central components of host defense mechanisms in a variety of species. One well conserved element in their signal transduction is Ser/Thr kinases, which couple early signaling events in a receptor complex at the plasma membrane to larger signalosomes in the cytosol. The fruit fly Drosophila melanogaster has one member of this family of kinases, termed Pelle. The complexity of this pathway is vastly increased in vertebrates, and several Pelle homologs have been described and termed IL-1 receptor-associated kinase (IRAK). Here we report the identification of a novel and distinct member of the IRAK family, IRAK-4. IRAK-4 is the closest human homolog to Pelle. Endogenous IRAK-4 interacts with IRAK-1 and TRAF6 in an IL-1-dependent manner, and overexpression of IRAK-4 can activate NF-kappa B as well as mitogen-activated protein (MAP) kinase pathways. Most strikingly, and in contrast to the other IRAKs, IRAK-4 depends on its kinase activity to activate NF-kappa B. In addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant-negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK-1, suggesting a role of IRAK-4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAK-1. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 99 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2002-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Drosophila Proteins JNK Mitogen-Activated Protein Kinases Phosphotransferases (Alcohol Group Acceptor) Chemistry Metabolism Protein Kinases Physiology Protein-Serine-Threonine Kinases Amino Acid Sequence Animals Blotting, Northern Cloning, Molecular DNA, Complementary Drosophila Melanogaster Enzyme Activation Genes, Reporter Immunoblotting Interleukin-1 Interleukin-1 Receptor-Associated Kinases MAP Kinase Kinase 4 MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Molecular Sequence Data Multigene Family NF-kappa B Phosphorylation Polymerase Chain Reaction Precipitin Tests Protein Binding Genetics Proteins Receptors, Interleukin-1 Recombinant Proteins Signal Transduction TNF Receptor-Associated Factor 6 Time Factors Tissue Distribution Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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