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Article

  • The EMBO Journal (2008) 27, 1333 - 1344
  • doi:10.1038/emboj.2008.62

Published online: 27 March 2008

The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development

Yogesh Kulathu1, Elias Hobeika1, Gleb Turchinovich1 and Michael Reth1

  1. Faculty of Biology, Max-Planck Institute for Immunobiology, University of Freiburg, Freiburg, Germany

Correspondence to:

Michael Reth, Faculty of Biology, Max-Planck Institute for Immunobiology, University of Freiburg, Stuebeweg 51, Freiburg D-79108, Germany. Tel.: +49 761 5108420; Fax: +49 761 5108423; E-mail: reth@immunbio.mpg.de

Received 18 September 2007; Accepted 3 March 2008

Upon B-cell antigen receptor (BCR) activation, the protein tyrosine kinase Syk phosphorylates the adaptor protein SH2 domain-containing leukocyte protein of 65 kDa (SLP-65), thus coupling the BCR to diverse signalling pathways. Here, we report that SLP-65 is not only a downstream target and substrate of Syk but also a direct binding-partner and activator of this kinase. This positive feedback is mediated by the binding of the SH2 domain of SLP-65 to an autophosphorylated tyrosine of Syk. The mutant B cells that cannot form the Syk/SLP-65 complex are defective in BCR-induced extracellular signal-regulated kinase, nuclear factor kappa B and nuclear factor of activated T cells, but not Akt activation, and are blocked in B-cell development. Furthermore, we show that formation of the Syk/SLP-65 complex is required for sustained Ca2+ responses in activated B cells. We suggest that after activation and internalization of the BCR, Syk remains active as part of a membrane-bound Syk/SLP-65 complex controlling sustained signalling and calcium influx.

  • Keywords:

    • adaptors,
    • B-cell antigen receptor signalling,
    • calcium,
    • lymphocyte development,
    • tyrosine kinase