A Double-Edged Kinase Lyn: A Positive and Negative Regulator for Antigen Receptor–mediated Signals |
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| Authors: | Hirofumi Nishizumi Keisuke Horikawa Irena Mlinaric-Rascan and Tadashi Yamamoto |
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| Institution: | From the *Department of Oncology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; and the ?Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan |
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| Abstract: | B cells from young lyn−/− mice are hyperresponsive to anti-IgM–induced proliferation, suggesting involvement of Lyn in negative regulation of B cell antigen receptor (BCR)-mediated signaling. Here we show that tyrosine phosphorylation of FcγRIIB and CD22 coreceptors, which are important for feedback suppression of BCR-induced signaling, was severely impaired in lyn−/− B cells upon their coligation with the BCR. Hypophosphorylation on tyrosine residues of these molecules resulted in failure of recruiting the tyrosine phosphatase SHP-1 and inositol phosphatase SHIP, SH2-containing potent inhibitors of BCR-induced B cell activation, to the coreceptors. Consequently, lyn−/− B cells exhibited defects in suppressing BCR-induced Ca2+ influx and proliferation. Thus, Lyn is critically important in tyrosine phosphorylation of the coreceptors, which is required for feedback suppression of B cell activation. |
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