Paired immunoglobulin-like receptor (PIR)-A is involved in activating mast cells through its association with Fc receptor γ chain

A Maeda, M Kurosaki, T Kurosaki - The Journal of experimental …, 1998 - rupress.org
A Maeda, M Kurosaki, T Kurosaki
The Journal of experimental medicine, 1998rupress.org
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 …
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 γ 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 γ chain, whereas PIR-B mediates the inhibitory signal through its ITIMs.
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