Abstract
Upon B-cell activation, the signaling subunits Ig-α and Ig-β of the B-cell antigen receptor become phosphorylated not only on tyrosines but also on serine residues. Using a specific antibody, we show that serine 197 (S197) in the cytoplasmic tail of Ig-α is phosphorylated upon B-cell antigen receptor activation, and that this modification inhibits the signal output of the B-cell antigen receptor. Surprisingly, we found that the well-known protein tyrosine kinase Syk (spleen tyrosine kinase) phosphorylates S197 on Ig-α, thus not only activating but also inhibiting signaling from the B-cell antigen receptor. This finding identifies Syk as a dual-specificity kinase and establishes a previously unexplored paradigm for the self-regulation of biological signaling processes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism*
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CD79 Antigens / chemistry
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CD79 Antigens / genetics
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CD79 Antigens / metabolism
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Cell Line
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Drosophila
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Transgenic
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Phosphorylation
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Protein-Tyrosine Kinases / chemistry
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Antigen, B-Cell / chemistry
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Serine / chemistry
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Signal Transduction
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Structural Homology, Protein
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Syk Kinase
Substances
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CD79 Antigens
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Cd79a protein, mouse
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Intracellular Signaling Peptides and Proteins
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Receptors, Antigen, B-Cell
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Recombinant Proteins
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Serine
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse