© 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
Paired Immunoglobulin-like Receptor (PIR)-A Is Involved in Activating Mast Cells through Its Association with Fc Receptor
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
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
chain, whereas PIR-B mediates the inhibitory signal through its ITIMs.
Key Words: activation signal Fc receptor
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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