Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium.
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.
Quinn
T P
TP
Cardiovascular Research Institute, University of California, San Francisco 94143.
Peters
K G
KG
De Vries
C
C
Ferrara
N
N
Williams
L T
LT
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
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