Properties of two VEGF receptors, Flt-1 and KDR, in signal transduction

Ann N Y Acad Sci. 2000 May;902:201-5; discussion 205-7. doi: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Endothelial Growth Factors / pharmacology
  • Endothelial Growth Factors / physiology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Lymphokines / pharmacology
  • Lymphokines / physiology*
  • Matrix Metalloproteinase 1 / genetics
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-ets
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, Growth Factor / physiology*
  • Receptors, Vascular Endothelial Growth Factor
  • Signal Transduction / physiology*
  • Transcription Factors / genetics
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors

Substances

  • ETS1 protein, human
  • Endothelial Growth Factors
  • Lymphokines
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Receptors, Growth Factor
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1
  • Matrix Metalloproteinase 1