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

Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T
Nature. 1995 378 (6554): 303-6

PMID: 7477353 · DOI:10.1038/378303a0

The Syk cytoplasmic protein-tyrosine kinase has two amino-terminal SH2 domains and a carboxy-terminal catalytic domain. Syk, and its close relative ZAP-70, are apparently pivotal in coupling antigen- and Fc-receptors to downstream signalling events. Syk associates with activated Fc receptors, the T cell receptor complex and the B-cell antigen-receptor complex (BCR) in immature and mature B lymphocytes. 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 alpha and beta-chains of the BCR, leading to Syk activation. 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.

MeSH Terms (25)

Animals B-Lymphocytes Base Sequence Bone Marrow Cells Cell Differentiation Clone Cells DNA Primers Enzyme Precursors Exons Fetal Death Fetal Viability Hematopoietic Stem Cell Transplantation Hemorrhage Humans Intracellular Signaling Peptides and Proteins Liver Mice Molecular Sequence Data Mutagenesis Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Protein-Tyrosine Kinases Receptors, Antigen, B-Cell Signal Transduction Syk Kinase

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