| First Author | Nunomura S | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 4 | Pages | 1205-17 |
| PubMed ID | 20101614 | Mgi Jnum | J:159195 |
| Mgi Id | MGI:4441568 | Doi | 10.1002/eji.200939651 |
| Citation | Nunomura S, et al. (2010) FcepsilonRI beta-chain ITAM amplifies PI3K-signaling to ensure synergistic degranulation response via FcepsilonRI and adenosine receptors. Eur J Immunol 40(4):1205-17 |
| abstractText | 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. |
