Human type II Fcgamma receptors inhibit B cell activation by interacting with the p21(ras)-dependent pathway.
Abstract
Co-ligation of antigen receptors and type II Fcgamma receptors (FcgammaRIIb) on B cells interrupts signal transduction and ultimately inhibits antibody production. We have identified p52 Shc in the FcgammaRIIb1-specific immunoprecipitates isolated from the membrane fraction of BL41 Burkitt lymphoma cells following B cell receptor-FcgammaRIIb1 co-ligation. The insolubilized synthetic peptide representing the phosphorylated form of the tyrosine-based inhibitory motif of FcgammaRIIb also binds Shc from the lysates of activated but not from resting BL41 cells. This suggests that the binding does not depend on the interaction of FcgammaRIIb1-phosphotyrosine with the SH2 domain of Shc. Tyr phosphorylation of FcgammaRIIb1-associated Shc is low, indicating an impaired function. Shc is implicated in regulating p21(ras) activation; thus, we have compared p21(ras) activities in BL41 cells treated in different ways. p21(ras) activity is reduced when B cell receptor and FcgammaRIIb1 are co-ligated. p21(ras) couples protein-tyrosine kinase-dependent events to the Ser/Thr kinase-mediated signaling pathway leading to the activation of mitogen-activated protein kinases (MAPK). Our results show that B cell receptor-FcgammaRIIb1 co-cross-linking ...Continue Reading
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B cell Activation
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