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PMID:7477353
| Citation |
Cheng, AM, Rowley, B, Pao, W, Hayday, A, Bolen, JB and Pawson, T (1995) Syk tyrosine kinase required for mouse viability and B-cell development. Nature 378:303-6 |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1038/378303a0 |
| Keywords |
Animals; B-Lymphocytes/cytology; B-Lymphocytes/enzymology; Base Sequence; Bone Marrow Cells; Cell Differentiation/physiology; Clone Cells; DNA Primers; Enzyme Precursors/genetics; Enzyme Precursors/metabolism; Exons; Fetal Death; Fetal Viability/physiology; Hematopoietic Stem Cell Transplantation; Hemorrhage/embryology; Humans; Intracellular Signaling Peptides and Proteins; Liver/cytology; Liver/embryology; Mice; Molecular Sequence Data; Mutagenesis; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Protein-Tyrosine Kinases/genetics; Protein-Tyrosine Kinases/metabolism; Receptors, Antigen, B-Cell/metabolism; Signal Transduction |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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