RRC ID 11855
Author Nunomura S, Gon Y, Yoshimaru T, Kashiwakura J, Kawakami T, Ra C.
Title FcepsilonRI beta-chain ITAM amplifies PI3K-signaling to ensure synergistic degranulation response via FcepsilonRI and adenosine receptors.
Journal Eur. J. Immunol.
Abstract Simultaneous stimulation with antigen and adenosine in mast cells induces a synergistic degranulation response at a low antigen dose that is insufficient to cause secretion by itself. This kind of stimulation is thought to be relevant to the immediate asthmatic response upon bronchial challenge with low-dose allergen. In this context, FcepsilonRI- and adenosine receptor-mediated signalings cooperate to increase degranulation in mast cells. In the present study, we prepared mast cells that have mutations (Y219F/Y225F/Y229F) in three tyrosine residues of the FcepsilonRI beta-chain (FcRbeta)-ITAM in order to elucidate the molecular mechanisms of degranulation response synergistically elicited by costimulation with low-dose antigen and adenosine. Introduction of mutations in the FcRbeta-ITAM abolished the synergistic degranulation response. Upon costimulation with low-dose antigen and adenosine, tyrosine phosphorylation of Grb2-associated binder 2, which is located upstream of PI3K-signaling, was significantly increased, but severely diminished in FcRbeta-ITAM mutant cells. These findings indicate that FcRbeta acts as a critical element in mast cell synergistic degranulation response through FcepsilonRI and adenosine receptors, and that PI3K-signaling through FcRbeta-ITAM is a crucial participant in augmentation of FcepsilonRI-mediated degranulation by adenosine.
Volume 40(4)
Pages 1205-17
Published 2010-4
DOI 10.1002/eji.200939651
PMID 20101614
MeSH Adenosine / pharmacology Animals Calcium Signaling / physiology Cell Degranulation / physiology* Immunoglobulin E / immunology Mast Cells / physiology* Mice Mice, Inbred Strains Mice, Knockout Mutagenesis, Site-Directed Phosphatidylinositol 3-Kinases / physiology* Phosphoproteins / metabolism Phosphorylation Phosphotyrosine / analysis Protein Processing, Post-Translational Protein Structure, Tertiary Receptor Cross-Talk / physiology* Receptors, IgE / genetics Receptors, IgE / physiology* Receptors, Purinergic P1 / physiology* Recombinant Fusion Proteins / metabolism Signal Transduction / physiology*
IF 4.248
Times Cited 7
Mice Fyn Targeting mice