Functionally active VEGF fusion proteins.

M V Backer; J M Backer

doi:10.1006/prep.2001.1472

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PubMed · 11570839

Functionally active VEGF fusion proteins.

M V Backer·J M Backer

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Abstract

Angiogenesis is stimulated by vascular endothelial growth factor (VEGF) acting via endothelial cell-specific receptors, such as VEGFR-2, that are overexpressed at the sites of angiogenesis. If VEGF retains activity as a fusion protein with a large N-terminal extension, it would facilitate development of VEGF-based vehicles for receptor-mediated delivery of therapeutic and diagnostic agents to the sites of angiogenesis. We have constructed, expressed in Escherichia coli, and purified VEGF fusion proteins containing a 158-amino acid N-terminal extension fused to human VEGF(121), VEGF(165), and VEGF(189). We report here that VEGF fusion proteins induce tyrosine autophosphorylation of VEGFR-2 and its downstream targets, as well as cell contraction in cells overexpressing VEGFR-2. Although N-terminal extensions decrease the affinity of VEGF fusion proteins to VEGFR-2, at saturating concentrations these proteins are as efficient as correct size VEGF(165). We hypothesize that VEGF fusion proteins may be employed for targeting endothelial cells at the sites of angiogenesis.

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Amino Acid Sequence Cell Line, Transformed Cell Size Drug Design Endothelial Growth Factors Humans Lymphokines Molecular Sequence Data Phosphorylation Protein Binding Protein Isoforms Receptor Protein-Tyrosine Kinases Receptors, Growth Factor Receptors, Vascular Endothelial Growth Factor Recombinant Fusion Proteins Signal Transduction Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Journal Article

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M V Backer, J M Backer. 2001. Functionally active VEGF fusion proteins.. https://doi.org/10.1006/prep.2001.1472

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