| pubmed-article:17337443 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C0021755 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C0670896 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C1701950 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C1150423 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C1546857 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C1556066 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C1619636 | lld:lifeskim |
| pubmed-article:17337443 | lifeskim:mentions | umls-concept:C1514873 | lld:lifeskim |
| pubmed-article:17337443 | pubmed:issue | 18 | lld:pubmed |
| pubmed-article:17337443 | pubmed:dateCreated | 2007-4-30 | lld:pubmed |
| pubmed-article:17337443 | pubmed:abstractText | 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. | lld:pubmed |
| pubmed-article:17337443 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17337443 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17337443 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:17337443 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17337443 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17337443 | pubmed:month | May | lld:pubmed |
| pubmed-article:17337443 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:17337443 | pubmed:author | pubmed-author:GlückAntonA | lld:pubmed |
| pubmed-article:17337443 | pubmed:author | pubmed-author:GramHermannH | lld:pubmed |
| pubmed-article:17337443 | pubmed:author | pubmed-author:MathisonJohn... | lld:pubmed |
| pubmed-article:17337443 | pubmed:author | pubmed-author:KinzelBerndB | lld:pubmed |
| pubmed-article:17337443 | pubmed:author | pubmed-author:MüllerMatthia... | lld:pubmed |
| pubmed-article:17337443 | pubmed:author | pubmed-author:DavisChristop... | lld:pubmed |
| pubmed-article:17337443 | pubmed:author | pubmed-author:Koziczak-Holb... | lld:pubmed |
| pubmed-article:17337443 | pubmed:author | pubmed-author:JoyceClaireC | lld:pubmed |
| pubmed-article:17337443 | pubmed:author | pubmed-author:TschoppClaude... | lld:pubmed |
| pubmed-article:17337443 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17337443 | pubmed:day | 4 | lld:pubmed |
| pubmed-article:17337443 | pubmed:volume | 282 | lld:pubmed |
| pubmed-article:17337443 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17337443 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17337443 | pubmed:pagination | 13552-60 | lld:pubmed |
| pubmed-article:17337443 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:17337443 | pubmed:meshHeading | pubmed-meshheading:17337443... | lld:pubmed |
| pubmed-article:17337443 | pubmed:year | 2007 | lld:pubmed |
| pubmed-article:17337443 | pubmed:articleTitle | IRAK-4 kinase activity is required for interleukin-1 (IL-1) receptor- and toll-like receptor 7-mediated signaling and gene expression. | lld:pubmed |
| pubmed-article:17337443 | pubmed:affiliation | Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. | lld:pubmed |
| pubmed-article:17337443 | pubmed:publicationType | Journal Article | lld:pubmed |
| entrez-gene:266632 | entrezgene:pubmed | pubmed-article:17337443 | lld:entrezgene |
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