| First Author | Nunomura S | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 8 | Pages | 4052-64 |
| PubMed ID | 22430736 | Mgi Jnum | J:184055 |
| Mgi Id | MGI:5320209 | Doi | 10.4049/jimmunol.1102796 |
| Citation | Nunomura S, et al. (2012) The FcRbeta- and gamma-ITAMs play crucial but distinct roles in the full activation of mast cells induced by IgEkappa and Protein L. J Immunol 188(8):4052-64 |
| abstractText | Previous studies suggested that Protein L (PpL), the bacterial Ig-binding protein, activates mast cells. PpL presumably performs the activation by interacting with membrane-bound IgEkappa, but the underlying mechanisms behind the process remain unclear. In the current study, we found that cell-surface FcepsilonRI expression is a critical factor participant in PpL-mediated full activation of murine mast cells, which includes cytokine production, the degranulation response, and leukotriene C(4) (LTC(4)) release, and that engagement of the FcepsilonRI with IgEkappa and PpL is enough to induce tyrosine phosphorylation of ITAM in the FcRbeta- and gamma-signaling subunits. Introduction of mutations in two canonical tyrosine residues (Y47F/Y58F) of the FcRgamma-ITAM completely abolished the above-mentioned mast cell functions, with the exception of LTC(4) release. Importantly, the FcRbeta-ITAM acts as a signal transducer that is responsible for LTC(4) release independently of the FcRgamma-ITAM. Taken together, our results suggest crucial and distinct functions for the FcRbeta- and gamma-ITAMs in the FcepsilonRI-dependent full activation of mast cells induced by IgEkappa and PpL. |
