Properties of two VEGF receptors, Flt-1 and KDR, in signal transduction.
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.
Sato
Y
Y
Department of Vascular Biology, Tohoku University, Sendai, Japan. y-sato@idac.tohoku.ac.jp
Kanno
S
S
Oda
N
N
Abe
M
M
Ito
M
M
Shitara
K
K
Shibuya
M
M
D016228:Endothelial Growth Factors / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology / Q000502:physiology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000502:physiology*; D040262:Receptors, Vascular Endothelial Growth Factor; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
C494041:ETS1 protein, human; D016228:Endothelial Growth Factors; D008222:Lymphokines; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D017978:Receptors, Growth Factor; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D020781:Matrix Metalloproteinase 1