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Association of C-Type Lectin Mincle with FcεRIβγ Subunits Leads to Functional Activation of RBL-2H3 Cells through Syk
- Source :
- Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Macrophage-inducible C-type lectin (Mincle) interacts with the γ-subunit of high-affinity IgE receptor (FcεRIγ) and activates Syk by recognizing its specific ligand, trehalose-6,6′-dimycolate, a glycolipid produced by Mycobacterium tuberculosis. It has been suggested that mast cells participate in the immune defense against pathogenic microbes including M. tuberculosis, although the functions are still uncertain. In this study, we examined the Mincle-mediated signaling pathway and cellular responses using RBL-2H3 cells. Mincle formed a protein complex with not only FcεRIγ but also FcεRIβ in a stable cell line expressing myc-tagged Mincle. In addition, engagement of Mincle increased the levels of protein tyrosine phosphorylation and ERK phosphorylation. A pull-down assay demonstrated that cross-linking of Mincle induced binding of FcεRIβγ subunits to the Src homology 2 domain of Syk. Pharmacological and genetic studies indicated that activation of Syk was critical for Mincle-mediated activation of phospholipase Cγ2, leading to the activation of ERK and nuclear factor of activated T cells. Moreover, engagement of Mincle efficiently induced up-regulation of characteristic mast cell genes in addition to degranulation. Taken together, our present results suggest that mast cells contribute to Mincle-mediated immunity through Syk activation triggered by association with the FcεRIβγ complex.
- Subjects :
- 0301 basic medicine
Syk
Cell Degranulation
Article
Cell Line
03 medical and health sciences
chemistry.chemical_compound
C-type lectin
medicine
Animals
Syk Kinase
Lectins, C-Type
Mast Cells
Phosphorylation
Receptors, Immunologic
Extracellular Signal-Regulated MAP Kinases
Phosphotyrosine
Multidisciplinary
NFATC Transcription Factors
Phospholipase C gamma
Receptors, IgE
Degranulation
Tyrosine phosphorylation
Mast cell
Rats
Cell biology
Enzyme Activation
Protein Subunits
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
chemistry
Mutation
Signal transduction
Protein Binding
Signal Transduction
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....42af158743c98f67c1ee5c34f0db3122
- Full Text :
- https://doi.org/10.1038/srep46064