Requirement of the tyrosines at residues 258 and 270 of MAIR-I in inhibitory effect on degranulation from basophilic leukemia RBL-2H3.
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.
Okoshi
Yasushi
Y
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan.
Tahara-Hanaoka
Satoko
S
Nakahashi
Chigusa
C
Honda
Shin-ichiro
S
Miyamoto
Akitomo
A
Kojima
Hiroshi
H
Nagasawa
Toshiro
T
Shibuya
Kazuko
K
Shibuya
Akira
A
D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001491:Basophils / Q000276:immunology*; D015550:Cell Degranulation / Q000502:physiology*; D045744:Cell Line, Tumor; D007073:Immunoglobulin E / Q000276:immunology; D015471:Leukemia, Basophilic, Acute; D008407:Mast Cells / Q000276:immunology*; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000037:antagonists & inhibitors / Q000276:immunology*; D019056:Receptors, Polymeric Immunoglobulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C477367:MAIR-I, rat; D017455:Receptors, IgE; D019056:Receptors, Polymeric Immunoglobulin; D007073:Immunoglobulin E; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases