Tp. Quinn et al., FETAL LIVER KINASE-1 IS A RECEPTOR FOR VASCULAR ENDOTHELIAL GROWTH-FACTOR AND IS SELECTIVELY EXPRESSED IN VASCULAR ENDOTHELIUM, Proceedings of the National Academy of Sciences of the United Statesof America, 90(16), 1993, pp. 7533-7537
Vascular endothelial growth factor (VEGF), also known as vascular perm
eability factor, induces endothelial proliferation in vitro and vascul
ar permeability in vivo. The human transmembrane c-fms-like tyrosine k
inase Flt-1 has recently been identified as a VEGF receptor. Flt-1 kin
ase has seven immunoglobulin-like extracellular domains and a kinase i
nsert sequence, features shared by two other human gene-encoded protei
ns, 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 func
tional VEGF receptor. Flk-1 binds VEGF with high affinity, undergoes a
utophosphorylation, and mediates VEGF-dependent Ca2+ efflux in Xenopus
oocytes injected with Flk-1 mRNA. We also demonstrate by in situ hybr
idization that Flk-1 protein expression in the mouse embryo is restric
ted to the vascular endothelium and the umbilical cord stroma. VEGF an
d its receptors Flk-1/KDR and Flt-1 may play a role in vascular develo
pment and regulation of vascular permeability.