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

SYSNO ASEP	0370093
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Btk is a positive regulator in the TREM-1/DAP12 signaling pathway
Author(s)	Ormsby, Tereza (UMG-J) Schlecker, E. (DE) Ferdin, J. (DE) Tessarz, A.S. (DE) Angelisová, Pavla (UMG-J)_RID Koprulu, A.D. (AT) Borte, M. (DE) Warnatz, K. (DE) Schulze, I. (DE) Ellmeier, W. (DE) Hořejší, Václav (UMG-J)_RID Cerwenka, A. (DE)
Source Title	Blood. - : American Society of Hematology - ISSN 0006-4971 Roč. 118, č. 4 (2011), s. 936-945
Number of pages	10 s.
Language	eng - English
Country	US - United States
Keywords	TREM-1 ; DAP-12 ; Btk
Subject RIV	EB - Genetics ; Molecular Biology
R&D Projects	1M0506 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
CEZ	AV0Z50520514 - UMG-J (2005-2011)
UT WOS	000293221700020
DOI	10.1182/blood-2010-11-317016
Annotation	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.
Workplace	Institute of Molecular Genetics
Contact	Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217
Year of Publishing	2012

Number of the records: 1