title: FcεRI-induced mast cell cytokine production critically involves an aspartic acid residue (D234) in the C-terminal intracellular domain of the FcεRIβ chain.
abstract: The high affinity IgE Fc receptor (FcεRI) β chain is well implicated as a signal amplifier through the immunoreceptor tyrosine-based activation motif (ITAM) in its C-terminal intracellular region. Our previous study, however, demonstrated that mutation in all of the three tyrosine residues within the FcεRIβ ITAM did not impair FcεRI-induced cytokine production, suggesting a possible functional region other than the ITAM. To investigate the ITAM-independent mechanism by which FcεRIβ regulates FcεRI-induced cytokine production, mouse mast cells expressing various FcεRIβ mutants were generated. We observed that truncation of the FcεRIβ C-terminus downstream of the ITAM resulted in a considerable decrease in FcεRI-induced IL-6 production but not degranulation. Furthermore, mutagenesis of a single C-terminal aspartic acid (D234) to alanine (β-D234A) also significantly impaired IL-6 production. In addition, the similarity between the circular dichroism (CD) spectra of the wild type and β-D234A suggests that the secondary structure of the FcεRIβ C-terminus was not affected by the D234A mutation. Consistently, we did not observe any effect of this mutation on FcεRI-induced tyrosine phosphorylation of FcεRIβ. These observations strongly suggest a novel signaling pathway mediated by the cytoplasmic tail downstream of the FcεRIβ ITAM.
authors.affiliation: Division of Molecular Cell Immunology and Allergology, Nihon University Graduate School of Medical Science, Tokyo, Japan.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Terada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nunomura
authors.forename: Toshibumi
authors.initials: T
authors.lastname: Shimokawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Murayama
authors.forename: Seiichi
authors.initials: S
authors.lastname: Era
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
authors.forename: Chisei
authors.initials: C
authors.lastname: Ra
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry / Q000235:genetics; D016207:Cytokines / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017455:Receptors, IgE / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; C521907:Fc-epsilon receptor I beta-chain, mouse; D017455:Receptors, IgE; D001224:Aspartic Acid