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http://purl.uniprot.org/citations/12874245http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12874245http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12874245http://www.w3.org/2000/01/rdf-schema#comment"We have developed a novel LPS probe using a highly purified and homogenous preparation of [(3)H] Escherichia coli LPS from the deep rough mutant, which contains a covalently linked, photoactivable 4-p-(azidosalicylamido)-butylamine group. This cross-linker was used to identify the LPS-binding proteins in membranes of the murine-macrophage-like cell line RAW 264.7. The alpha-subunit (PSMA1 C2, 29.5 kDa) and the beta-subunit (PSMB4 N3, 24.36 kDa) of the 20S proteasome complex were identified as LPS-binding proteins. This is the first report demonstrating LPS binding to enzymes such as the proteasome subunits. Functionally, LPS enhanced the chymotrypsin-like activity of the proteasome to degrade synthetic peptides in vitro and, conversely, the proteasome inhibitor lactacystin completely blocked the LPS-induced proteasome's chymotrypsin activity as well as macrophage TNF-alpha secretion and the expression of multiple inflammatory mediator genes. Lactacystin also completely blocked the LPS-induced expression of Toll-like receptor 2 mRNA. In addition, lactacystin dysregulated mitogen-activated protein kinase phosphorylation in LPS-stimulated macrophages, but failed to inhibit IL-1 receptor-associated kinase-1 activity. Importantly, lactacystin also prevented LPS-induced shock in mice. These data strongly suggest that the proteasome complex regulates the LPS-induced signal transduction and that it may be an important therapeutic target in Gram-negative sepsis."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.org/dc/terms/identifier"doi:10.4049/jimmunol.171.3.1515"xsd:string
http://purl.uniprot.org/citations/12874245http://purl.org/dc/terms/identifier"doi:10.4049/jimmunol.171.3.1515"xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Shen J."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Shen J."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Zhang G."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Zhang G."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Qureshi N."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Qureshi N."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Vogel S.N."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Vogel S.N."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Lenschat A."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Lenschat A."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Morrison D.C."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Morrison D.C."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Perera P.-Y."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Perera P.-Y."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Splitter G."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/author"Splitter G."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/name"J. Immunol."xsd:string
http://purl.uniprot.org/citations/12874245http://purl.uniprot.org/core/name"J. Immunol."xsd:string