title: Association of C-Type Lectin Mincle with FcεRIβγ Subunits Leads to Functional Activation of RBL-2H3 Cells through Syk.
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.
authors.affiliation: Third Department of Internal Medicine, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.|Division of Genome Science and Microbiology, Department of Pathological Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Honjoh
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.|Life Science Innovation Center, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Chihara
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Hatsumi
authors.initials: H
authors.lastname: Yoshiki
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.|Life Science Innovation Center, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Yamauchi
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.|Life Science Innovation Center, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.|Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Clinical Laboratories, University of Fukui Hospital, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hida
authors.affiliation: Third Department of Internal Medicine, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ishizuka
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.|Life Science Innovation Center, University of Fukui, 23-3 Matsuoka-Shimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Kiyonao
authors.initials: K
authors.lastname: Sada
mesh_terms: D000818:Animals; D015550:Cell Degranulation; D002460:Cell Line; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D037181:Lectins, C-Type / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology; D009154:Mutation / Q000235:genetics; D050778:NFATC Transcription Factors / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism*; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase / Q000378:metabolism*
chemical_list: C000629138:Clec4e protein, rat; C553474:FCER1A protein, rat; D037181:Lectins, C-Type; D050778:NFATC Transcription Factors; D021122:Protein Subunits; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D019000:Phosphotyrosine; D000072377:Syk Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D051966:Phospholipase C gamma