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

Yogesh Kulathu, Elias Hobeika, Gleb Turchinovich, Michael Reth

    Research output: Contribution to journalArticle

    62 Citations (Scopus)

    Abstract

    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 Ca(2+) 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.
    Original languageEnglish
    Pages (from-to)1333-44
    Number of pages12
    JournalEMBO Journal
    Volume27
    Issue number9
    DOIs
    Publication statusPublished - 7 May 2008

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