Syk is a dual-specificity kinase that self-regulates the signal output from the B-cell antigen receptor
Syk is a dual-specificity kinase that self-regulates the signal output from the B-cell antigen receptor
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.
- Max Planck Society Germany
- University of Freiburg Germany
Mice, Knockout, Models, Molecular, B-Lymphocytes, Mice, Inbred BALB C, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Receptors, Antigen, B-Cell, Mice, Transgenic, Protein-Tyrosine Kinases, Recombinant Proteins, Cell Line, Mice, Mutation, Serine, Animals, Drosophila, Amino Acid Sequence, Phosphorylation, CD79 Antigens, Signal Transduction
Mice, Knockout, Models, Molecular, B-Lymphocytes, Mice, Inbred BALB C, Molecular Sequence Data, Intracellular Signaling Peptides and Proteins, Receptors, Antigen, B-Cell, Mice, Transgenic, Protein-Tyrosine Kinases, Recombinant Proteins, Cell Line, Mice, Mutation, Serine, Animals, Drosophila, Amino Acid Sequence, Phosphorylation, CD79 Antigens, Signal Transduction
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