A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals.
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.
Nishizumi
H
H
Department of Oncology, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Horikawa
K
K
Mlinaric-Rascan
I
I
Yamamoto
T
T
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules; D018390:Gene Targeting; D037102:Lectins; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000172:deficiency / Q000378:metabolism*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; C080571:Fc gamma receptor IIB; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D051918:Sialic Acid Binding Ig-like Lectin 2; D014443:Tyrosine; D019061:src-Family Kinases