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Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1

Oncogene volume 18, pages 2291–2297 (1999)Cite this article

Abstract

Coligation of paired immunoglobulin-like receptor B (PIR-B) with B cell antigen receptor (BCR) blocks antigen-induced B cell activation. This inhibition is mediated in part by recruitment of SHP-1 and SHP-2 to the phosphorylated ITIMs in the cytoplasmic domain of PIR-B; however the molecular target(s) of these phosphatases remain elusive. Here we show that PIR-B ligation inhibits the BCR-induced tyrosine phosphorylation of Igα/Igβ, Syk, Btk and phospholipase C (PLC)-γ2. Overexpression of a catalytically inactive form of SHP-1 prevents the PIR-B-mediated inhibition of tyrosine phosphorylation of Syk, Btk, and PLC-γ2. Dephosphorylation of Syk and Btk mediated by SHP-1 leads to a decrease of their kinase activity, which in turn inhibits tyrosine phosphorylation of PLC-γ2. Furthermore, we define a requirement for Lyn in mediating tyrosine phosphorylation of PIR-B. Based on these results, we propose a model of PIR-B-mediated inhibitory signaling in which coligation of PIR-B and BCR results in phosphorylation of ITIMs by Lyn, subsequent recruitment of SHP-1, and a resulting inhibition of the BCR-induced inositol 1,4,5-trisphosphate generation by dephosphorylation of Syk and Btk.

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Acknowledgements

We would like to acknowledge M Kurosaki for the technical assistance, Dr H Umemori and Dr T Yamamoto for providing anti-Lyn Ab, and Dr S Arai (Fujisaki institute, Hayashibara Biochemical Laboratories Inc.) for generation of anti-Btk mAb 43-3B. This work was supported by grants to TK from the Ministry of Education, Science, Sports, and Culture of Japan, the Uehara Memorial Foundation, and the Sumitomo Foundation.

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Authors and Affiliations

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

    Akito Maeda & Tomohiro Kurosaki

  2. Laboratory of Allergy and Immunology, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts, 02215, USA

    Andrew M Scharenberg & Jean-Pierre Kinet

  3. Department of Medicine III, Osaka University Medical School, 565, Osaka, Japan

    Satoshi Tsukada

  4. Hoechst Marion Roussel, Bridgewater, New Jersey, 08807, USA

    Joseph B Bolen

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  1. Akito Maeda
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Maeda, A., Scharenberg, A., Tsukada, S. et al. Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1. Oncogene 18, 2291–2297 (1999). https://doi.org/10.1038/sj.onc.1202552

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