Author/Editor		Nishizumi, Hirofumi; Horikawa, Keisuke; Mlinarič-Raščan, Irena; Yamamoto, Tadashi
Title		A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals
Type		članek
Source		J Exp Med
Vol. and No.		Letnik 187, št. 8
Publication year		1998
Volume		str. 1343-8
Language		eng
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.
Descriptors		SRC-FAMILY KINASES B-LYMPHOCYTES RECEPTORS, ANTIGEN, B-CELL ANTIGENS, CD ANTIGENS, DIFFERENTIATION, B-LYMPHOCYTE GENE TARGETING LYMPHOCYTE TRANSFORMATION MICE, MUTANT STRAINS MUTAGENESIS PHOSPHORYLATION RECEPTORS, IGG SIGNAL TRANSDUCTION TYROSINE