Btk is a positive regulator in the TREM-1/DAP12 signaling pathway

0370093 - ÚMG 2012 RIV US eng J - Článek v odborném periodiku
Ormsby, Tereza - Schlecker, E. - Ferdin, J. - Tessarz, A.S. - Angelisová, Pavla - Koprulu, A.D. - Borte, M. - Warnatz, K. - Schulze, I. - Ellmeier, W. - Hořejší, Václav - Cerwenka, A.
Btk is a positive regulator in the TREM-1/DAP12 signaling pathway.
Blood. Roč. 118, č. 4 (2011), s. 936-945. ISSN 0006-4971. E-ISSN 1528-0020
Grant CEP: GA MŠMT 1M0506
Výzkumný záměr: CEZ:AV0Z50520514
Klíčová slova: TREM-1 * DAP-12 * Btk
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 9.898, rok: 2011

TREM-1 receptor 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. We demonstrate that Bruton tyrosine kinase (Btk), becomes phosphorylated upon TREM-1 triggering. In 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. 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.Intact membrane localization and a functional kinase domain were required for TREM-1-mediated signaling. After TREM-1 engagement, TNF-α production by PBMCs was reduced in the patients suffering from XLA, a disease caused by mutations in the BTK gene.
Trvalý link: http://hdl.handle.net/11104/0203997