Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium

Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7533-7. doi: 10.1073/pnas.90.16.7533.


Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, induces endothelial proliferation in vitro and vascular permeability in vivo. The human transmembrane c-fms-like tyrosine kinase Flt-1 has recently been identified as a VEGF receptor. Flt-1 kinase has seven immunoglobulin-like extracellular domains and a kinase insert sequence, features shared by two other human gene-encoded proteins, kinase insert domain-containing receptor (KDR) and FLT-4. In this study we show that the mouse homologue of KDR, Flk-1, is a second functional VEGF receptor. Flk-1 binds VEGF with high affinity, undergoes autophosphorylation, and mediates VEGF-dependent Ca2+ efflux in Xenopus oocytes injected with Flk-1 mRNA. We also demonstrate by in situ hybridization that Flk-1 protein expression in the mouse embryo is restricted to the vascular endothelium and the umbilical cord stroma. VEGF and its receptors Flk-1/KDR and Flt-1 may play a role in vascular development and regulation of vascular permeability.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Antisense Elements (Genetics)
  • Base Sequence
  • Calcium / metabolism
  • Cell Line
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / enzymology*
  • Female
  • Fetus
  • Gene Expression
  • In Situ Hybridization
  • Kinetics
  • Liver / enzymology*
  • Lymphokines / metabolism*
  • Mice
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Vascular Endothelial Growth Factor
  • Transfection
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Xenopus


  • Antisense Elements (Genetics)
  • Endothelial Growth Factors
  • Lymphokines
  • Oligodeoxyribonucleotides
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • Calcium