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

First Author  Nishizumi H Year  1998
Journal  J Exp Med Volume  187
Issue  8 Pages  1343-8
PubMed ID  9547345 Mgi Jnum  J:110932
Mgi Id  MGI:3652425 Doi  10.1084/jem.187.8.1343
Citation  Nishizumi H, et al. (1998) A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals. J Exp Med 187(8):1343-8
abstractText  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.
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