PMID:18369315

Citation	Kulathu, Y, Hobeika, E, Turchinovich, G and Reth, M (2008) The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development. EMBO J. 27:1333-44
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.
Links	PubMed PMC2374840 Online version:10.1038/emboj.2008.62
Keywords	Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Calcium/metabolism; Calcium Signaling/genetics; Calcium Signaling/physiology; Cell Differentiation; Cell Line; Extracellular Signal-Regulated MAP Kinases/genetics; Extracellular Signal-Regulated MAP Kinases/metabolism; Flow Cytometry; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Luciferases/genetics; Luciferases/metabolism; Mice; Mice, Knockout; Models, Biological; Mutation; NF-kappa B/genetics; NF-kappa B/metabolism; Phosphorylation; Protein Binding; Protein-Tyrosine Kinases/genetics; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; Receptors, Antigen, B-Cell/genetics; Receptors, Antigen, B-Cell/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Transfection; Tyrosine/genetics; Tyrosine/metabolism; src Homology Domains/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:KSYK	involved_in	GO:0045579: positive regulation of B cell differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:KSYK		GO:0045579: positive regulation of B cell differentiation	ECO:0000315:		P		figure 4	complete CACAO 6490
HUMAN:KSYK		GO:0004672: protein kinase activity	ECO:0000314:		F		figure 3	complete CACAO 6491

References

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