Inhibitory and stimulatory functions of paired Ig-like receptor (PIR) family in RBL-2H3 cells.
In this study, we demonstrate potent regulatory function of the murine killer cell inhibitory receptor-like molecules, paired Ig-like receptors (PIRs) or p91, using chimeric receptors expressed on the rat basophilic leukemia cell line RBL-2H3. One of the chimeras, which has the transmembrane and cytoplasmic domain of PIR-B fused to the extracellular portion of type IIB receptor for IgG, was able to inhibit the type I receptor for IgE-mediated degranulation response upon coaggregation. This chimera also suppressed cytoplasmic Ca2+ mobilization in the presence and absence of calcium ion in the extracellular medium. Tyrosine to phenylalanine point mutations at the third and fourth immunoreceptor tyrosine-based inhibitory motif-like sequences of PIR-B attenuated the inhibitory effects on degranulation and on cytoplasmic Ca2+ mobilization, indicating the important role of these tyrosines for the delivery of negative signal. In contrast, the cross-linking of another chimeric receptor composed of the type IIB receptor for IgG extracellular portion and the transmembrane and short cytoplasmic sequence of PIR-A elicited Ca2+ mobilization and degranulation. These results indicate that PIR molecules may regulate cellular functions both positively and negatively.
Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi.
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Y
Yamashita
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Ono
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T
Takai
D000818:Animals; D002118:Calcium / Q000378:metabolism; D007136:Immunoglobulins / Q000276:immunology; D007942:Leukemia, Experimental / Q000276:immunology* / Q000378:metabolism; D008969:Molecular Sequence Data; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured
D007136:Immunoglobulins; C105948:Pira1 protein, mouse; C105949:Pirb protein, mouse; C491380:Pirb protein, rat; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D002118:Calcium