Novel Peptides Selected to Bind Vascular Endothelial Growth Factor Target the Receptor-Binding Site

Biochemistry ◽  
1998 ◽  
Vol 37 (51) ◽  
pp. 17754-17764 ◽  
Author(s):  
Wayne J. Fairbrother ◽  
Hans W. Christinger ◽  
Andrea G. Cochran ◽  
Germaine Fuh ◽  
Christopher J. Keenan ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Binding Site ◽  
Receptor Binding ◽  
Vascular Endothelial ◽  
Receptor Binding Site ◽  
Endothelial Growth Factor

Up-regulation of vascular endothelial growth factor receptor Flt-1 after endothelial denudation: role of transcription factor Egr-1

Blood ◽  
2000 ◽  
Vol 95 (11) ◽  
pp. 3387-3395
Author(s):  
Felipe Vidal ◽  
Julián Aragonés ◽  
Arántzazu Alfranca ◽  
Manuel O. de Landázuri
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Binding Site ◽  
Vascular Injury ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Transcription Analysis ◽  
Endothelial Denudation ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is highly expressed in vascular remodeling processes and accelerates reendothelialization after mechanical denudation. Two VEGF tyrosine kinase receptors have been reported—fms-like–tyrosine kinase-1 (Flt-1) and kinase domain region (KDR). Little is known about the regulation of the expression of these receptors after vascular injury. Herein, we have analyzed the expression of Flt-1 after mechanical denudation of primary cultures of endothelial cells, which has been considered a useful in vitro model to study endothelium responses to vascular injury. After denudation, the Flt-1 protein and mRNA levels are clearly up-regulated, and transient transfection experiments showed a strong induction of theflt-1 promoter-dependent transcription. Analysis of the flt-1 promoter sequence revealed the presence of a putative binding site for the early growth response factor-1 (Egr-1) at positions −24 to −16. Electrophoretic mobility shift and supershift assays showed that Egr-1 was able to bind to this DNA sequence, and cotransfection of the flt-1 promoter reporter plasmid with an Egr-1 expression vector resulted in enhancement of its transcriptional activity. Furthermore, the mutation of the Egr-1 binding site markedly reduced the denudation-induced flt-1promoter activity. These data demonstrate that Flt-1 is up-regulated after endothelial denudation and that Egr-1 plays a relevant role in this process.

Inhibition of receptor binding by high-affinity RNA ligands to vascular endothelial growth factor

Biochemistry ◽  
1994 ◽  
Vol 33 (34) ◽  
pp. 10450-10456 ◽  
Author(s):  
Derek Jellinek ◽  
Louis S. Green ◽  
Carol Bell ◽  
Nebojsa Janjic
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Receptor Binding ◽  
Vascular Endothelial ◽  
High Affinity ◽  
Rna Ligands ◽  
Endothelial Growth Factor
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