Differential binding characteristics and cellular inhibition by soluble VEGF receptors 1 and 2

被引:115
作者
Roeckl, W
Hecht, D
Sztajer, H
Waltenberger, J
Yayon, A
Weich, HA
机构
[1] GBF, Dept Gene Regulat & Differentiat, D-38124 Braunschweig, Germany
[2] GBF, Dept Enzymol, D-38124 Braunschweig, Germany
[3] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
[4] Univ Ulm, Sch Med, D-89081 Ulm, Germany
关键词
VEGF; KDR; FLT-1; endothelial cells; soluble receptors; angiogenesis; heparin;
D O I
10.1006/excr.1998.4039
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The FLT-1 and KDR genes encode transmembrane tyrosine kinases which function as high-affinity receptors for vascular endothelial growth factor (VEGF). We have used the baculovirus system to express the extracellular parts of the FLT-1 receptor and KDR receptor in soluble form (sFLT-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 sKDR can neither compete with the binding of VEGF(165) to human endothelial cells carrying both receptors nor block VEGF(165) induced mitogenicity. Soluble KDR only partially inhibits cell migration even at high concentrations, in contrast to sFLT which can almost completely block (82%) VEGF-induced cell proliferation and migration. Taken together these results show that the two soluble VEGF receptor proteins, sFLT-1 and sKDR, despite binding the same ligand, behave very differently when immobilized with regard to their dependence on heparin for VEGF binding. In solution their respective ability to function as receptor antagonists is also strikingly different, possibly a reflection of their different dependency on heparin. (C) 1998 Academic Press.
引用
收藏
页码:161 / 170
页数:10
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