A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling Journal Article


Authors: Muta, T.; Kurosaki, T.; Misulovin, Z.; Sanchez, M.; Nussenzweig, M. C.; Ravetch, J. V.
Article Title: A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling
Abstract: THE Fc receptor on B lymphocytes, FcγRIIB (β1 isoform), helps to modulate B-cell activation triggered by the surface immunoglobulin complex 1,2. Crosslinking of membrane immunoglobulin by antigen or anti-Ig F(ab′;)2 antibody induces a transient increase in cytosolic free Ca2+, a rise in inositol-3-phosphate, activation of protein kinase C, and enhanced protein tyrosine phosphorylation3-5. Crosslinking FcγRIIB with the surface immunoglobulin complex confers a dominant signal that prevents or aborts lymphocyte activation triggered through the ARH-1 motifs of the signal transduction subunits Ig-α and Ig-β. Here we show that FcγRIIB modulates membrane immunoglobulin-induced Ca2+ mobilization by inhibiting Ca2+ influx, without changing the pattern of tyrosine phosphorylation. A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB is both necessary and sufficient for this effect. Tyrosine at residue 309 in this motif is phosphorylated upon co-crosslinking with surface immunoglobulin; mutation of this residue aborts the inhibitory effect of FcγRIIB. This inhibition is directly coupled to signalling mediated through Ig-α and Ig-β as evidenced by chimaeric IgM/α and IgM/β molecules. The 13-residue motif in FcyRIIB controls lymphocyte activation by inhibiting a Ca2+ sig-nalling pathway triggered through ARH-1 motifs as a result of recruitment of novel SH2-containing proteins that interact with this FcγRIIB cytoplasmic motif. © 1994 Nature Publishing Group.
Keywords: signal transduction; human cell; animals; mice; calcium; tumor cells, cultured; transfection; tyrosine; phosphorylation; b lymphocyte; b-lymphocytes; lymphocyte activation; amino acid sequence; molecular sequence data; lymphoma; cytoplasm; receptors, igg; antigens, cd; point mutation; receptors, antigen, b-cell; cross linking; calcium mobilization; lymphocyte receptor; immunoglobulin fc fragment; human; priority journal; article
Journal Title: Nature
Volume: 368
Issue: 6466
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 1994-03-03
Start Page: 70
End Page: 73
Language: English
DOI: 10.1038/368070a0
PROVIDER: scopus
PUBMED: 8107887
DOI/URL:
Notes: Source: Scopus
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  1. Jeffrey V. Ravetch
    72 Ravetch