Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation

Nature. 1995 Jul 6;376(6535):70-4. doi: 10.1038/376070a0.


Tie-1 and Tie-2 define a new class of receptor tyrosine kinases that are specifically expressed in developing vascular endothelial cells. To study the functions of Tie-1 and Tie-2 during vascular endothelial cell growth and differentiation in vivo, targeted mutations of the genes in mice were introduced by homologous recombination. Embryos deficient in Tie-1 failed to establish structural integrity of vascular endothelial cells, resulting in oedema and subsequently localized haemorrhage. However, analyses of embryos deficient in Tie-2 showed that it is important in angiogenesis, particularly for vascular network formation in endothelial cells. This result contrasts with previous reports on Tie-2 function in vasculogenesis and/or endothelial cell survival. Our in vivo analyses indicate that the structurally related receptor tyrosine kinases Tie-1 and Tie-2 have important but distinct roles in the formation of blood vessels.

MeSH terms

  • Animals
  • Base Sequence
  • Blood Vessels / embryology*
  • Blood Vessels / growth & development
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cell Line
  • DNA Primers
  • Edema / embryology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / embryology*
  • Hemorrhage / embryology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutagenesis
  • Phenotype
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Receptors, TIE


  • DNA Primers
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-1
  • Receptor, TIE-2
  • Receptors, TIE