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J Exp Med. 1998 Apr 20;187(8):1343-8.

A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals.

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  • 1Department of Oncology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.

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 FcgammaRIIB 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.

PMID:
9547345
[PubMed - indexed for MEDLINE]
PMCID:
PMC2212230
Free PMC Article
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