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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Antisense Elements (Genetics)
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Base Sequence
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Calcium / metabolism
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Cell Line
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Endothelial Growth Factors / metabolism*
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Endothelium, Vascular / enzymology*
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Female
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Fetus
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Gene Expression
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In Situ Hybridization
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Kinetics
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Liver / enzymology*
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Lymphokines / metabolism*
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Mice
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Molecular Sequence Data
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Oligodeoxyribonucleotides
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Oocytes / drug effects
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Oocytes / metabolism
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Phosphorylation
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Protein-Tyrosine Kinases / biosynthesis
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Vascular Endothelial Growth Factor
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Transfection
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Xenopus
Substances
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Antisense Elements (Genetics)
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Endothelial Growth Factors
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Lymphokines
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Oligodeoxyribonucleotides
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Protein-Tyrosine Kinases
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Receptors, Vascular Endothelial Growth Factor
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Calcium