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

Nature. 1995 Nov 16;378(6554):303-6. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • Syk Kinase


  • DNA Primers
  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, B-Cell
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase
  • Syk protein, mouse