W. Roeckl et al., DIFFERENTIAL BINDING CHARACTERISTICS AND CELLULAR-INHIBITION BY SOLUBLE VEGF RECEPTOR-1 AND RECEPTOR-2, Experimental cell research, 241(1), 1998, pp. 161-170
The FLT-1 and KDR genes encode transmembrane tyrosine kinases which fu
nction as high-affinity receptors for vascular endothelial growth fact
or (VEGF). We have used the baculovirus system to express the extracel
lular parts of the FLT-1 receptor and KDR receptor in soluble form (sF
LT-1 and sKDR), for in vitro binding and competition assays. Here, we
show that the binding of VEGF(165) to sKDR but not sFLT-1 is dependent
on heparin, regardless of whether VEGF(165), or sKDR is immobilized.
Further, only sFLT-1 acts as a receptor antagonist in solution and sKD
R can neither compete with the binding of VEGF(165) to human endotheli
al cells carrying both receptors nor block VEGF(165) induced mitogenic
ity. Soluble KDR only partially inhibits cell migration even at high c
oncentrations, in contrast to sFLT which can almost completely block (
82%) VEGF-induced cell proliferation and migration. Taken together the
se results show that the two soluble VEGF receptor proteins, sFLT-1 an
d sKDR, despite binding the same ligand, behave very differently when
immobilized with regard to their dependence on heparin for VEGF bindin
g. In solution their respective ability to function as receptor antago
nists is also strikingly different, possibly a reflection of their dif
ferent dependency on heparin. (C) 1998 Academic Press.