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Syk is a dual-specificity kinase that self-regulates the signal output from the B-cell antigen receptor

Beate Heizmann1, Michael Reth, Simona Infantino

  • 1Centre for Biological Signalling Studies, BIOSS, University of Freiburg, 79104 Freiburg, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|October 14, 2010
PubMed

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.

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