The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/9/991/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 5, September 7, 1998 991-995


Brief Definitive Reports

Paired Immunoglobulin-like Receptor (PIR)-A Is Involved in Activating Mast Cells through Its Association with Fc Receptor {gamma} Chain

Akito Maeda, Mari Kurosaki, and Tomohiro Kurosaki

From the Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan

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.

Key Words: activation signal • Fc receptor {gamma} chain • immunoreceptor tyrosine-based activation motif • mast cell • paired immunoglobulin-like receptor A


Address correspondence to Tomohiro Kurosaki, Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan. Phone: 81-6-993-9445; Fax: 81-6-994-6099; E-mail: kurosaki{at}mxr.meshnet.or.jp

Note added in proof. The results that PIR-A is able to transmit a stimulatory signal have been obtained independently (Yamashita, Y., M. Ono, and T. Takai. J. Immunol. In press).


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