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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Reusch, P. Martiny-baron, G. Marmé, D. Siemeister, G. Schirner, M. Barleon, B. |
| Description | Author Affiliation: Siemeister G ( Institute of Molecular Medicine, Tumor Biology Center, Freiburg, Germany.); |
| Abstract | Vascular endothelial growth factor (VEGF) is a potent mitogen with a unique specificity for endothelial cells and a key mediator of aberrant endothelial cell proliferation and vascular permeability in a variety of human pathological situations, such as tumor angiogenesis, diabetic retinopathy, rheumatoid arthritis, or psoriasis. VEGF is a symmetric homodimeric molecule with two receptor binding interfaces lying on each pole of the molecule. Herein we report on the construction and recombinant expression of an asymmetric heterodimeric VEGF variant with an intact receptor binding interface at one pole and a mutant receptor binding interface at the second pole of the dimer. This VEGF variant binds to VEGF receptors but fails to induce receptor activation. In competition experiments, the heterodimeric VEGF variant antagonizes VEGF-stimulated receptor autophosphorylation and proliferation of endothelial cells. A 15-fold excess of the heterodimer was sufficient to inhibit VEGF-stimulated endothelial cell proliferation by 50%, and a 100-fold excess resulted in an almost complete inhibition. By using a rational approach that is based on the structure of VEGF, we have shown the feasibility to construct a VEGF variant that acts as an VEGF antagonist. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 95 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1998-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Endothelial Growth Factors Pharmacology Endothelium, Vascular Drug Effects Lymphokines Receptor Protein-Tyrosine Kinases Metabolism Receptors, Growth Factor Binding Sites Binding, Competitive Cell Division Cells, Cultured Cloning, Molecular Dimerization Biosynthesis Chemistry Cytology Genetic Variation Kinetics Models, Molecular Mutagenesis, Site-Directed Phosphorylation Receptors, Vascular Endothelial Growth Factor Recombinant Proteins Umbilical Arteries Umbilical Veins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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