| First Author | Nunomura S | Year | 2005 |
| Journal | Int Immunol | Volume | 17 |
| Issue | 6 | Pages | 685-94 |
| PubMed ID | 15944196 | Mgi Jnum | J:99534 |
| Mgi Id | MGI:3582901 | Doi | 10.1093/intimm/dxh248 |
| Citation | Nunomura S, et al. (2005) Role of the Fc{epsilon}RI {beta}-chain ITAM as a signal regulator for mast cell activation with monomeric IgE. Int Immunol 17(6):685-94 |
| abstractText | The beta-chain of the high-affinity receptor for IgE (FcepsilonRI) plays a crucial role for amplification of the intracellular signaling in mast cells upon FcepsilonRI cross-linking by IgE*antigen complexes (IgE*Ag). Some monomeric IgE as well as IgE*Ag stimulate FcepsilonRI-signaling pathways, leading to cell activation, whereas the biological functions of the beta-chain in the monomeric IgE-mediated mast cell signaling and responses are largely unknown. In the present study, FcepsilonRI is reconstituted with either wild-type beta-chain or mutated beta-chain immunoreceptor tyrosine-based activation motif (ITAM) employing retrovirus-mediated gene transfer into the FcepsilonRI beta-chain-/- mast cells. We demonstrated that the transfectants with mutated beta-chain ITAM stimulated with monomeric IgE sufficiently produce inflammatory cytokines, although degranulation, intracellular Ca(2+) mobilization and leukotriene C(4) synthesis are significantly reduced. Furthermore, analyses of molecular mechanisms of the signaling revealed that the expression of cytokine genes and activation of extracellular signal-regulated kinase 1/2 and protein kinase C were significantly delayed in the beta-chain ITAM mutant cells stimulated with monomeric IgE, suggesting that the beta-chain ITAM regulates kinetics of gene transcriptions and signaling pathways for cytokine production. These findings for the first time revealed the unique functions of the beta-chain ITAM in both chemical mediator release and cytokine production of mast cells upon monomeric IgE stimulation. |
