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Syk tyrosine kinase required for mouse viability and B-cell development

An Erratum to this article was published on 15 February 1996

Abstract

THE Syk cytoplasmic protein-tyrosine kinase has two amino-terminal SH2 domains and a carboxy-terminal catalytic domain1. Syk, and its close relative ZAP-70 (ref. 2), are apparently pivotal in coupling antigen- and Fc-receptors to downstream signalling events3,4. Syk associates with activated Fc receptors5, the T cell receptor complex6 and the B-cell antigen-receptor complex (BCR) in immature and mature B lymphocytes7. On receptor activation, the tandem SH2 domains of Syk bind dual phosphotyrosine sites in the conserved ITAM motifs of receptor signalling chains, such as the immunoglobulin α and β-chains of the BCR, leading to Syk activation3,4,8. Here we have investigated Syk function in vivo by generating a mouse strain with a targeted mutation in the syk gene. Homozygous syk mutants suffered severe haemorrhaging as embryos and died perinatally, indicating that Syk has a critical role in maintaining vascular integrity or in wound healing during embryogenesis. Analysis of syk−/− lymphoid cells showed that the syk mutation impaired the differentiation of B-lineage cells, apparently by disrupting signalling from the pre-BCR complex and thereby preventing the clonal expansion, and further maturation, of pre-B cells.

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Cheng, A., Rowley, B., Pao, W. et al. Syk tyrosine kinase required for mouse viability and B-cell development. Nature 378, 303–306 (1995). https://doi.org/10.1038/378303a0

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