International Immunology Advance Access published online on November 29, 2004
International Immunology, doi:10.1093/intimm/dxh187
© 2004 by The Japanese Society for Immunology
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1 Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan; Department of Clinical and Experimental Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
* To whom correspondence should be addressed. Mast cells and basophils express the high affinity receptor for IgE (Fc
Accepted October 19, 2004
Article
Requirement of the tyrosines at residues 258 and 270 of MAIR-I in inhibitory effect on degranulation from basophilic leukemia RBL-2H3
2 Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan
3 Department of Clinical and Experimental Hematology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan
Akira Shibuya, E-mail: ashibuya{at}md.tsukuba.ac.jp
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Abstract
RI) and play a central role for IgE-associated immediate hypersensitivity reactions and allergic disorders. Cross-linking of Fc
RI-bound IgE with multivalent antigen initiates the activation of mast cells and basophils, resulting in the degranulation from these cells. We have recently identified a novel inhibitory receptor, myeloid-associated immunoglobulin-like receptor (MAIR)-I, which is expressed on mast cells as well as other myeloid cell lineages. Co-ligation of Fc
RI and MAIR-I inhibits IgE-mediated degranulation from mast cells. However, MAIR-I-mediated signaling pathways involved in the inhibition remain undetermined. Here, we demonstrate that the transfectant of rat basophil leukemia RBL-2H3 expressing wild-type MAIR-I is tyrosine phosphorylated and recruits SHP-1 and SHIP upon cross-linking of MAIR-I. By using RBL-2H3 transfectants expressing variable mutant MAIR-I at Y233, Y258, Y270 and/or Y299, we further demonstrate that both Y258 and Y270, but not Y233 and Y299, were phosphorylated and were essentially required for inhibition of IgE-mediated degranulation from the RBL-2H3 transfectant.
RI; inhibitory signal; ITIM; mast cell.
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