| RRC ID |
11855
|
| 著者 |
Nunomura S, Gon Y, Yoshimaru T, Kashiwakura J, Kawakami T, Ra C.
|
| タイトル |
FcepsilonRI beta-chain ITAM amplifies PI3K-signaling to ensure synergistic degranulation response via FcepsilonRI and adenosine receptors.
|
| ジャーナル |
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.
|
| 巻・号 |
40(4)
|
| ページ |
1205-17
|
| 公開日 |
2010-4-1
|
| DOI |
10.1002/eji.200939651
|
| PMID |
20101614
|
| MeSH |
Adaptor Proteins, Signal Transducing
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 |
4.404
|
| 引用数 |
10
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC01000 |
