Syk tyrosine kinase required for mouse viability and B-cell development.
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.
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology*; D001483:Base Sequence; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000502:physiology; D002999:Clone Cells; D017931:DNA Primers; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D005313:Fetal Death; D005328:Fetal Viability / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006470:Hemorrhage / Q000196:embryology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase
D017931:DNA Primers; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse