title: The FcRβ- and γ-ITAMs play crucial but distinct roles in the full activation of mast cells induced by IgEκ and Protein L.
abstract: Previous studies suggested that Protein L (PpL), the bacterial Ig-binding protein, activates mast cells. PpL presumably performs the activation by interacting with membrane-bound IgEκ, but the underlying mechanisms behind the process remain unclear. In the current study, we found that cell-surface FcεRI expression is a critical factor participant in PpL-mediated full activation of murine mast cells, which includes cytokine production, the degranulation response, and leukotriene C(4) (LTC(4)) release, and that engagement of the FcεRI with IgEκ and PpL is enough to induce tyrosine phosphorylation of ITAM in the FcRβ- and γ-signaling subunits. Introduction of mutations in two canonical tyrosine residues (Y47F/Y58F) of the FcRγ-ITAM completely abolished the above-mentioned mast cell functions, with the exception of LTC(4) release. Importantly, the FcRβ-ITAM acts as a signal transducer that is responsible for LTC(4) release independently of the FcRγ-ITAM. Taken together, our results suggest crucial and distinct functions for the FcRβ- and γ-ITAMs in the FcεRI-dependent full activation of mast cells induced by IgEκ and PpL.
authors.affiliation: Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo 173-8610, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nunomura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawakami
authors.forename: Chisei
authors.initials: C
authors.lastname: Ra
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D007073:Immunoglobulin E / Q000494:pharmacology; D017997:Leukotriene C4 / Q000096:biosynthesis / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010766:Phosphorylation; D061251:Primary Cell Culture; D021122:Protein Subunits / Q000235:genetics / Q000276:immunology; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C521907:Fc-epsilon receptor I beta-chain, mouse; D021122:Protein Subunits; D017455:Receptors, IgE; D017997:Leukotriene C4; D007073:Immunoglobulin E; D014443:Tyrosine; D002118:Calcium