The Transmembrane Adaptor Protein SCIMP Facilitates Sustained Dectin-1 Signaling in Dendritic Cells.
J Biol Chem
; 291(32): 16530-40, 2016 08 05.
Article
em En
| MEDLINE
| ID: mdl-27288407
ABSTRACT
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 PLCγ1/2, 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Sistema de Sinalização das MAP Quinases
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Lectinas Tipo C
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Proteínas Adaptadoras de Transdução de Sinal
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2016
Tipo de documento:
Article