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| Subject Categories: Signal Transduction | Immunology |
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| The EMBO Journal
(2008) 27, 1333–1344, doi:10.1038/emboj.2008.62 Published online 27 March 2008 |
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| The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development |
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| Yogesh Kulathu, Elias Hobeika, Gleb Turchinovich and Michael Reth |
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Faculty of Biology, Max-Planck Institute for Immunobiology, University of Freiburg, Freiburg, Germany To whom correspondence should be addressed 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; Published online 27 March 2008. |
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| Abstract |
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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  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. |
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| Keywords: adaptors, B-cell antigen receptor signalling, calcium, lymphocyte development, tyrosine kinase |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSVav and the B cell signalosome Nature Immunology News and Views (01 Jun 2001) Checks and balances on developing B cells Nature Immunology News and Views (01 Jan 2003) RESEARCHImaging the Modulation of Adenoviral Kinetics and Biodistribution for Cancer Gene Therapy Molecular Therapy Original Article The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development The EMBO Journal Article |
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