Abstract
Vascular endothelial growth factor (VEGF) is a principal regulator of vasculogenesis and angiogenesis. VEGF expresses its effects by binding to two VEGF receptors, Flt-1 and KDR. However, properties of Flt-1 and KDR in the signal transduction of VEGF-mediated effects in endothelial cells (ECs) were not entirely clarified. We investigated this issue by using two newly developed blocking monoclonal antibodies (mAbs) against Flt-1 and KDR. VEGF elicits DNA synthesis and cell migration of human umbilical vein endothelial cells (HUVECs). The pattern of inhibition of these effects by two mAbs indicates that DNA synthesis is preferentially mediated by KDR. In contrast, the 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, which influences cell migration by regulating cell adhesion via the assembly of vinculin in focal adhesion plaque and tyrosine-phosphorylation of focal adhesion kinase (FAK) and paxillin.
MeSH Terms
3T3 Cells/drug effects,metabolism
Actins/metabolism,ultrastructure
Animals
Antibodies, Monoclonal/pharmacology
Cell Line
Cell Movement/drug effects
Cytoskeletal Proteins/metabolism
DNA/biosynthesis,drug effects
Endothelial Growth Factors/metabolism,pharmacology
Endothelium, Vascular/cytology,drug effects,metabolism
Enzyme Inhibitors/pharmacology
Flavonoids/pharmacology
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Humans
Imidazoles/pharmacology
Indoles/pharmacology
Lymphokines/metabolism,pharmacology
Maleimides/pharmacology
Mice
Mitogen-Activated Protein Kinase 1/antagonists & inhibitors,metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases/antagonists & inhibitors,metabolism
Paxillin
Phosphoproteins/metabolism
Phosphorylation
Protein-Tyrosine Kinases/metabolism
Proto-Oncogene Proteins/immunology,metabolism
Pyridines/pharmacology
Receptor Protein-Tyrosine Kinases/immunology,metabolism
Receptors, Growth Factor/immunology,metabolism
Receptors, Vascular Endothelial Growth Factor
Signal Transduction
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factors
Vinculin/metabolism
p38 Mitogen-Activated Protein Kinases
Chemicals
Actins
Antibodies, Monoclonal
Cytoskeletal Proteins
Endothelial Growth Factors
Enzyme Inhibitors
Flavonoids
Imidazoles
Indoles
Lymphokines
Maleimides
PXN protein, human
Paxillin
Phosphoproteins
Proto-Oncogene Proteins
Pxn protein, mouse
Pyridines
Receptors, Growth Factor
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Vinculin
DNA
Protein-Tyrosine Kinases
Receptor Protein-Tyrosine Kinases
Receptors, Vascular Endothelial Growth Factor
Vascular Endothelial Growth Factor Receptor-1
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
PTK2 protein, human
Ptk2 protein, mouse
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
bisindolylmaleimide I
SB 203580
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kanno S
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Oda N
Abe M
Terai Y
Ito M
Shitara K
Tabayashi K
Shibuya M
Sato Y
