Abstract
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
Substances
- 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