Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial calls

Vascular endothelial growth factor (VEGF) is a principal regulator of vascu logenesis and angiogenesis, VEGF expresses its effects by binding to two VE GF receptors, Flt-1 and KDR, However, properties of FI-l and KDR in the sig nal transduction of VEGF-mediated effects in endothelial cells (ECs) were n ot entirely clarified, We investigated this issue by using two newly develo ped blocking monoclonal antibodies (mAbs) against Flt-1 and KDR, VEGF elici ts DKA. synthesis and cell migration of human umbilical, vein endothelial c ells (HUVECs). The pattern of inhibition of these effects by two mAbs indic ates that DNA. synthesis is preferentially mediated by KDR, In contrast, th e regulation of cell migration by VEGF appears to be more complicated. Flt- 1 regulates cell, migration through modulating actin reorganization, which is essential for cell motility. a distinct signal is generated by KDR, whic h influences cell migration by regulating cell adhesion via the assembly of vinculin in focal adhesion plaque and tyrosine-phosphorylation of focal ad hesion kinase (FAK) and paxillin.