title: Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium.
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.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco 94143.
authors.forename: T P
authors.initials: TP
authors.lastname: Quinn
authors.forename: K G
authors.initials: KG
authors.lastname: Peters
authors.forename: C
authors.initials: C
authors.lastname: De Vries
authors.forename: N
authors.initials: N
authors.lastname: Ferrara
authors.forename: L T
authors.initials: LT
authors.lastname: Williams
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology*; D005260:Female; D005333:Fetus; D015870:Gene Expression; D017403:In Situ Hybridization; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008222:Lymphokines / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014981:Xenopus
chemical_list: D016375:Antisense Elements (Genetics); D016228:Endothelial Growth Factors; D008222:Lymphokines; D009838:Oligodeoxyribonucleotides; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D002118:Calcium