Number of the records: 1
The Transmembrane Adaptor Protein SCIMP Facilitates Sustained Dectin-1 Signaling in Dendritic Cells
- 1.
SYSNO ASEP 0472003 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The Transmembrane Adaptor Protein SCIMP Facilitates Sustained Dectin-1 Signaling in Dendritic Cells Author(s) Králová, Jarmila (UMG-J)
Fabišik, Matěj (UMG-J)
Pokorná, Jana (UMG-J)
Skopcová, Tereza (UMG-J)
Malissen, B. (FR)
Brdička, Tomáš (UMG-J) RID, ORCIDNumber of authors 6 Source Title Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 291, č. 32 (2016), s. 16530-16540Number of pages 11 s. Language eng - English Country US - United States Keywords beta-glucan receptor ; c-type lectin ; toll-like receptors ; fungal-infections ; antifungal immunity ; pattern-recognition ; candida-albicans ; erk activation ; mice ; innate Subject RIV EB - Genetics ; Molecular Biology R&D Projects GAP302/12/1712 GA ČR - Czech Science Foundation (CSF) Institutional support UMG-J - RVO:68378050 UT WOS 000380826700013 DOI https://doi.org/10.1074/jbc.M116.717157 Annotation Transmembrane adaptor proteins are molecules specialized in recruiting cytoplasmic proteins to the proximity of the cell membrane as part of the signal transduction process. A member of this family, SLP65/SLP76, Csk-interacting membrane protein (SCIMP), recruits a complex of SLP65/SLP76 and Grb2 adaptor proteins, known to be involved in the activation of PLC gamma 1/2, Ras, and other pathways. SCIMP expression is restricted to antigen-presenting cells. In a previous cell line-based study, it was shown that, in B cells, SCIMP contributes to the reverse signaling in the immunological synapse, downstream of MHCII glycoproteins. There it mainly facilitates the activation of ERK MAP kinases. However, its importance for MHCII glycoprotein-dependent ERK signaling in primary B cells has not been analyzed. Moreover, its role in macrophages and dendritic cells has remained largely unknown. Here we present the results of our analysis of SCIMP-deficient mice. In these mice, we did not observe any defects in B cell signaling and B cell-dependent responses. On the other hand, we found that, in dendritic cells and macrophages, SCIMP expression is up-regulated after exposure to GM-CSF or the Dectin-1 agonist zymosan. Moreover, we found that SCIMP is strongly phosphorylated after Dectin-1 stimulation and that it participates in signal transduction downstream of this important pattern recognition receptor. Our analysis of SCIMP-deficient dendritic cells revealed that SCIMP specifically contributes to sustaining long-term MAP kinase signaling and cytokine production downstream of Dectin-1 because of an increased expression and sustained phosphorylation lasting at least 24 h after signal initiation. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2017
Number of the records: 1