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Requirement of the tyrosines at residues 258 and 270 of MAIR-I in inhibitory effect on degranulation from basophilic leukemia RBL-2H3.

Abstract
Mast cells and basophils express the high affinity receptor for IgE (FcepsilonRI) and play a central role for IgE-associated immediate hypersensitivity reactions and allergic disorders. Cross-linking of FcepsilonRI-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 FcepsilonRI 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.
AuthorsYasushi Okoshi, Satoko Tahara-Hanaoka, Chigusa Nakahashi, Shin-ichiro Honda, Akitomo Miyamoto, Hiroshi Kojima, Toshiro Nagasawa, Kazuko Shibuya, Akira Shibuya
JournalInternational immunology (Int Immunol) Vol. 17 Issue 1 Pg. 65-72 (Jan 2005) ISSN: 0953-8178 [Print] England
PMID15569773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • MAIR-I, rat
  • Receptors, IgE
  • Receptors, Polymeric Immunoglobulin
  • Immunoglobulin E
  • Tyrosine
  • Protein Tyrosine Phosphatases
Topics
  • Amino Acid Substitution
  • Animals
  • Antibodies, Monoclonal (pharmacology)
  • Basophils (immunology)
  • Cell Degranulation (physiology)
  • Cell Line, Tumor
  • Immunoglobulin E (immunology)
  • Leukemia, Basophilic, Acute
  • Mast Cells (immunology)
  • Mutation (genetics)
  • Phosphorylation
  • Protein Tyrosine Phosphatases (metabolism)
  • Rats
  • Receptors, IgE (antagonists & inhibitors, immunology)
  • Receptors, Polymeric Immunoglobulin (chemistry, genetics, metabolism)
  • Tyrosine (genetics, metabolism)

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