FcεRI-induced mast cell cytokine production critically involves an aspartic acid residue (D234) in the C-terminal intracellular domain of the FcεRIβ chain

Biochem Biophys Res Commun. 2011 Jul 15;410(4):744-8. doi: 10.1016/j.bbrc.2011.06.030. Epub 2011 Jun 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aspartic Acid / chemistry
  • Aspartic Acid / genetics
  • Cytokines / immunology*
  • Mast Cells / immunology*
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Receptors, IgE / chemistry
  • Receptors, IgE / genetics
  • Receptors, IgE / immunology*

Substances

  • Cytokines
  • Fc-epsilon receptor I beta-chain, mouse
  • Receptors, IgE
  • Aspartic Acid