| http://purl.uniprot.org/citations/17337443 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17337443 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17337443 | http://www.w3.org/2000/01/rdf-schema#comment | "IRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Although regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function is still controversial. To investigate the role of IRAK-4 kinase function in vivo, "knock-in" mice were generated by replacing the wild type IRAK-4 gene with a mutant gene encoding kinase-deficient IRAK-4 protein (IRAK-4 KD). IRAK-4 kinase was rendered inactive by mutating the conserved lysine residues in the ATP pocket essential for coordinating ATP. Analyses of embryonic fibroblasts and macrophages obtained from IRAK-4 KD mice demonstrate lack of cellular responsiveness to stimulation with IL-1beta or a Toll-like receptor 7 (TLR7) agonist. IRAK-4 kinase deficiency prevents the recruitment of IRAK-1 to the IL-1 receptor complex and its subsequent phosphorylation and degradation. IRAK-4 KD cells are severely impaired in NFkappaB, JNK, and p38 activation in response to IL-1beta or TLR7 ligand. As a consequence, IL-1 receptor/TLR7-mediated production of cytokines and chemokines is largely absent in these cells. Additionally, microarray analysis identified IL-1beta response genes and revealed that the induction of IL-1beta-responsive mRNAs is largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in IL-1 receptor (IL-1R)/TLR7-mediated induction of inflammatory responses."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m700548200"xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m700548200"xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Muller M."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Muller M."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Gram H."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Gram H."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Kinzel B."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Kinzel B."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Joyce C."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Joyce C."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Mathison J.C."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Mathison J.C."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Davis C.N."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Davis C.N."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Gluck A."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Gluck A."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Koziczak-Holbro M."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Koziczak-Holbro M."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Tschopp C."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/author | "Tschopp C."xsd:string |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17337443 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |