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The kinase Syk as an adaptor controlling sustained calcium signalling and B‐cell development
Author(s) -
Kulathu Yogesh,
Hobeika Elias,
Turchinovich Gleb,
Reth Michael
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.62
Subject(s) - syk , biology , signal transducing adaptor protein , microbiology and biotechnology , signalling , kinase , calcium signaling , calcium , signal transduction , tyrosine kinase , medicine
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 κ 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.