Paired immunoglobulin-like receptor (PIR)-A is involved in activating mast cells through its association with Fc receptor gamma chain.
Paired immunoglobulin-like receptor (PIR)-A and PIR-B possess similar ectodomains with six immunoglobulin-like loops, but have distinct transmembrane and cytoplasmic domains. PIR-B bears immunoreceptor tyrosine-based inhibitory motif (ITIM) sequences in its cytoplasmic domain that recruit Src homology (SH)2 domain-containing tyrosine phosphatases SHP-1 and SHP-2, leading to inhibition of B and mast cell activation. In contrast, the PIR-A protein has a charged Arg residue in its transmembrane region and a short cytoplasmic domain that lacks ITIM sequences. Here we show that Fc receptor gamma chain, containing an immunoreceptor tyrosine-based activation motif (ITAM), associates with PIR-A. Cross-linking of this PIR-A complex results in mast cell activation such as calcium mobilization in an ITAM-dependent manner. Thus, our data provide evidence for the existence of two opposite signaling pathways upon PIR aggregation. PIR-A induces the stimulatory signal by using ITAM in the associated gamma chain, whereas PIR-B mediates the inhibitory signal through its ITIMs.
Maeda
A
A
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan.
Kurosaki
M
M
Kurosaki
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002645:Chickens; D006801:Humans; D046911:Macromolecular Substances; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D046911:Macromolecular Substances; C105948:Pira1 protein, mouse; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases