A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases

Marlene Meyer, Matthias Clauss, Albrecht Lepple-Wienhues, Johannes Waltenberger, Hellmut G. Augustin, Marina Ziche, Christa Lanz, Mathias Büttner, Hanns Joachim Rziha, Christoph Dehio

Research output: Contribution to journalArticle

386 Citations (Scopus)

Abstract

The different members of the vascular endothelial growth factor (VEGF) family act as key regulators of endothelial cell function controlling vasculogenesis, angiogenesis, vascular permeability and endothelial cell survival. In this study, we have functionally characterized a novel member of the VEGF family, designated VEGF-E. VEGF-E sequences are encoded by the parapoxvirus Orf virus (OV). They carry the characteristic cysteine knot motif present in all mammalian VEGFs, while forming a microheterogenic group distinct from previously described members of this family. VEGF-E was expressed as the native protein in mammalian cells or as a recombinant protein in Escherichia coli and was shown to act as a heat-stable, secreted dimer. VEGF-E and VEGF-A were found to possess similar bioactivities, i.e. both factors stimulate the release of tissue factor (TF), the proliferation, chemotaxis and sprouting of cultured vascular endothelial cells in vitro and angiogenesis in vivo. Like VEGF-A, VEGF-E was found to bind with high affinity to VEGF receptor-2 (KDR) resulting in receptor autophosphorylation and a biphasic rise in free intracellular Ca2+ concentration, whilst in contrast to VEGF-A, VEGF-E did not bind to VEGF receptor-1 (Flt-1). VEGF-E is thus a potent angiogenic factor selectively binding to VEGF receptor-2. These data strongly indicate that activation of VEGF receptor-2 alone can efficiently stimulate angiogenesis.

Original languageEnglish (US)
Pages (from-to)363-374
Number of pages12
JournalEMBO Journal
Volume18
Issue number2
DOIs
StatePublished - Jan 15 1999
Externally publishedYes

Fingerprint

Orf virus
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Receptor Protein-Tyrosine Kinases
Viruses
Vascular Endothelial Growth Factor A
Endothelial cells
Endothelial Cells
Parapoxvirus
Vascular Endothelial Growth Factors
Angiogenesis Inducing Agents
Capillary Permeability
Thromboplastin
Chemotaxis
Bioactivity

Keywords

  • Angiogenesis
  • Flt-1
  • KDR
  • Orf virus
  • VEGF

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases. / Meyer, Marlene; Clauss, Matthias; Lepple-Wienhues, Albrecht; Waltenberger, Johannes; Augustin, Hellmut G.; Ziche, Marina; Lanz, Christa; Büttner, Mathias; Rziha, Hanns Joachim; Dehio, Christoph.

In: EMBO Journal, Vol. 18, No. 2, 15.01.1999, p. 363-374.

Research output: Contribution to journalArticle

Meyer, Marlene ; Clauss, Matthias ; Lepple-Wienhues, Albrecht ; Waltenberger, Johannes ; Augustin, Hellmut G. ; Ziche, Marina ; Lanz, Christa ; Büttner, Mathias ; Rziha, Hanns Joachim ; Dehio, Christoph. / A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases. In: EMBO Journal. 1999 ; Vol. 18, No. 2. pp. 363-374.
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