Properties of Two VEGF Receptors, Flt‐1 and KDR, in Signal Transductiona
- 1 May 2000
- journal article
- review article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 902 (1), 201-207
- https://doi.org/10.1111/j.1749-6632.2000.tb06314.x
Abstract
The properties of two VEGF receptors, Flt‐1 and KDR, in the signal transduction of VEGF in human umbilical vein endothelial cells (HUVECs) were investigated by using two newly developed blocking monoclonal antibodies (mAbs) against Flt‐1 and KDR. VEGF stimulated the expression of transcription factor Ets‐1 as well as matrix metalloproteinase‐1 (MMP‐1) and Flt‐1 in HUVECs. The KDR/Flt‐1 heterodimer and the KDR homodimer mediate the expression of Ets‐1, MMP‐1, and Flt‐1. VEGF also stimulated DNA synthesis and migration of HUVECs. DNA synthesis is mediated by the same signaling system as the expression of Ets‐1. In contrast, cell migration is regulated by two distinct signaling systems. The Flt‐1 homodimer is required for actin reorganization. The KDR/Flt‐1 heterodimer and the KDR homodimer are required for the assembly of vinculin in focal adhesion plaque by regulating the phosphorylation of focal adhesion kinase (FAK) and paxillin.Keywords
This publication has 19 references indexed in Scilit:
- Roles of two VEGF receptors, Flt-1 and KDR, in the signal transduction of VEGF effects in human vascular endothelial cellsOncogene, 2000
- Induction of Ets-1 in endothelial cells during reendothelialization after denuding injuryJournal of Cellular Physiology, 1998
- Mechanisms of angiogenesisNature, 1997
- A cAMP Response Element and an Ets Motif Are Involved in the Transcriptional Regulation of flt-1 Tyrosine Kinase (Vascular Endothelial Growth Factor Receptor 1) GeneJournal of Biological Chemistry, 1996
- Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endotheliumNature, 1995
- Failure of blood-island formation and vasculogenesis in Flk-1-deficient miceNature, 1995
- Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factorBiochemical and Biophysical Research Communications, 1992
- The fms -Like Tyrosine Kinase, a Receptor for Vascular Endothelial Growth FactorScience, 1992
- Vascular Permeability Factor, an Endothelial Cell Mitogen Related to PDGFScience, 1989
- Vascular Endothelial Growth Factor Is a Secreted Angiogenic MitogenScience, 1989