Constitutive tyrosine phosphorylation of the inhibitory paired Ig-like receptor PIR-B.
PIR-A and PIR-B are activating and inhibitory Ig-like receptors on murine B lymphocytes, dendritic cells, and myeloid-lineage cells. The inhibitory function of PIR-B is mediated via its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs, whereas PIR-A pairs with the Fc receptor common gamma chain to form an activating receptor complex. In these studies, we observed constitutive tyrosine phosphorylation of PIR-B molecules on macrophages and B lymphocytes, irrespective of the cell activation status. Splenocyte PIR-B molecules were constitutively associated with the SHP-1 protein tyrosine phosphatase and Lyn protein tyrosine kinase. In Lyn-deficient mice, PIR-B tyrosine phosphorylation was greatly reduced. Unexpectedly, tyrosine phosphorylation of PIR-B was not observed in most myeloid and B cell lines but could be induced by ligation of the PIR molecules. Finally, the phosphorylation status of PIR-B was significantly reduced in MHC class I-deficient mice, although not in mice deficient in TAP1 or MHC class II expression. These findings suggest a physiological inhibitory role for PIR-B that is regulated by endogenous MHC class I-like ligands.
Ho
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Division of Developmental Immunology, University of Alabama at Birmingham, Birmingham, AL 35294-3300, USA.
Uehara
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Chen
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Kubagawa
H
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Cooper
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D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011971:Receptors, Immunologic / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D014443:Tyrosine