http://purl.uniprot.org/citations/21659545 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/21659545 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/21659545 | http://www.w3.org/2000/01/rdf-schema#comment | "The triggering receptor expressed on myeloid cells 1 (TREM-1) has been implicated in the production of proinflammatory cytokines and chemokines during bacterial infection and sepsis. For downstream signal transduction, TREM-1 is coupled to the ITAM-containing adaptor DAP12. Here, we demonstrate that Bruton tyrosine kinase (Btk), a member of the Tec kinases, becomes phosphorylated upon TREM-1 triggering. In U937-derived cell lines, in which expression of Btk was diminished by shRNA-mediated knockdown, phosphorylation of Erk1/2 and PLCγ1 and Ca²⁺ mobilization were reduced after TREM-1 stimulation. Importantly, TREM-1-induced production of the pro-inflammatory cytokines, TNF-α and IL-8, and up-regulation of activation/differentiation cell surface markers were impaired in Btk knockdown cells. Similar results were obtained upon TREM-1 stimulation of BMDCs of Btk(-/-) mice. The analysis of cells containing Btk mutants revealed that intact membrane localization and a functional kinase domain were required for TREM-1-mediated signaling. Finally, after TREM-1 engagement, TNF-α production by PBMCs was reduced in the majority of patients suffering from X-linked agammaglobulinemia (XLA), a rare hereditary disease caused by mutations in the BTK gene. In conclusion, our data identify Btk as a positive regulator in the ITAM-mediated TREM-1/DAP12 pathway and suggest its implication in inflammatory processes."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2010-11-317016"xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2010-11-317016"xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Warnatz K."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Warnatz K."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Angelisova P."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Angelisova P."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Horejsi V."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Horejsi V."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Ellmeier W."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Ellmeier W."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Cerwenka A."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Cerwenka A."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Schulze I."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Schulze I."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Ormsby T."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Ormsby T."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Borte M."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Borte M."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Ferdin J."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Ferdin J."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Koepruelue A.D."xsd:string |
http://purl.uniprot.org/citations/21659545 | http://purl.uniprot.org/core/author | "Koepruelue A.D."xsd:string |