Analysis of Biological Effects and Signaling Properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2)

By H. Gille, J. Kowalski, Bing Li, J. Lecouter, B. Moffat, T. F. Zioncheck, N. Pelletier, N. Ferrara. Journal of Biological Chemistry, 2001

651 citations recorded by the source corpus.

Endothelial cells express two related vascular endothelial growth factor (VEGF) receptor tyrosine kinases, KDR (kinase-insert domain containing receptor, or VEGFR-2) and Flt-1 (fms-like tyrosine kinase, or VEGFR-1). Although considerable experimental evidence links KDR activation to endothelial cell mitogenesis, there is still significant uncertainty concerning the role of individual VEGF receptors for other biological effects such as vascular permeability. VEGF mutants that bind to either KDR or Flt-1 with high selectivity were used to determine which of the two receptors serves to mediate different VEGF functions. In addition to mediating mitogenic signaling, selective KDR activation was sufficient for the activation of intracellular signaling pathways implicated in cell migration. KDR stimulation caused tyrosine phosphorylation of both phosphatidylinositol 3-kinase and phospholipase Cγ in primary endothelial cells and stimulated cell migration. KDR-selective VEGF was also able to induce angiogenesis in the rat cornea to an extent indistinguishable from wild type VEGF. We also demonstrate that KDR, but not Flt-1, stimulation is responsible for the induction of vascular permeability by VEGF.

Subfields: Cellular and Molecular Neuroscience, Immunology and Allergy, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f1110c29072fc20ddeaf2139f32052a1f46a40e2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. R. Roskoski
2. Rakesh K. Jain

In Immunology and Allergy

1. N. Ferrara
2. R. Roskoski

In Molecular Biology

1. R. Roskoski
2. N. Ferrara
3. Rakesh K. Jain
4. A. Adamis
5. Peter Carmeliet
6. H. Gerber

Citations in the corpus

• Vascular endothelial growth factor (VEGF) signaling in tumor progression. (2007, background): “VEGFR2, which has a molecular weight of about 210 kDa [53], is the predominant mediator of VEGF-stimulated endothelial cell migration, proliferation, survival, and enhanced vascular permeability [126-128].”
• Role of vascular endothelial growth factor in regulation of physiological angiogenesis. (2001, background): “In further support of this conclusion, VEGF mutants that bind selectively to Flk-1/KDR are able to induce mitogenesis and chemotaxis in normal endothelial and angiogenesis, as well as permeability, in vivo (46, 61).”