Characterization of the endothelium-specific murine vascular endothelial growth factor receptor-2 (Flk-1) promoter.

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  • Additional Information
    • Source:
      Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print Cited Medium: Print ISSN: 0009-7330 (Print) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res Subsets: MEDLINE
    • Publication Information:
      Publication: Baltimore, MD : Lippincott Williams & Wilkins
      Original Publication: Baltimore, Md. Grune & Stratton.
    • Subject Terms:
      Promoter Regions, Genetic*; Endothelium, Vascular/*metabolism ; Mice/*genetics ; Receptor Protein-Tyrosine Kinases/*genetics ; Receptors, Growth Factor/*genetics; Animals ; Base Sequence ; Cattle ; Cell Line ; Cloning, Molecular ; Molecular Probes/genetics ; Molecular Sequence Data ; Polymerase Chain Reaction ; Receptors, Vascular Endothelial Growth Factor ; Transcription, Genetic
    • Abstract:
      Flk-1, a high-affinity signaling receptor for vascular endothelial growth factor (VEGF), is strongly and specifically expressed on endothelial cells during embryonic development of the vascular system and during tumor angiogenesis. Disruption of Flk-1 gene function has recently been shown to prevent completely endothelial cell differentiation during murine embryonic development. To gain insights into the mechanisms that regulate the endothelium-specific Flk-1 expression, we have isolated the 5'-flanking region of the murine Flk-1 gene. RNase protection and primer extension analyses revealed a single transcriptional start site located 299 bp upstream from the translational start site in an initiator-like pyrimidine-rich sequence. The 5'-flanking region is rich in GC residues and lacks a typical TATA or CAAT box. A luciferase reporter construct containing a fragment from nucleotides -1900 to +299 showed strong endothelium-specific activity in transfected bovine aortic endothelial cells. Deletion analyses revealed that endothelium-specific Flk-1 expression is stimulated by the 5'-untranslated region of the first exon, which contains an activating element between nucleotides +137 and +299. In addition, two endothelium-specific negative regulatory elements were identified between nucleotides -4100 and -623. Two strong general activating elements were present in the region between nucleotides -96 and -37, which contains one potential NF kappa B and three potential AP-2 binding sites. This study shows that Flk-1 expression in endothelial cells is mainly regulated by an endothelium-specific activating element in the long 5'-untranslated region of the first exon and by negative regulatory elements located further upstream.
    • Accession Number:
      0 (Molecular Probes)
      0 (Receptors, Growth Factor)
      EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
      EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
    • Publication Date:
      Date Created: 19960801 Date Completed: 19961212 Latest Revision: 20190706
    • Publication Date:
      20250114
    • Accession Number:
      10.1161/01.res.79.2.277
    • Accession Number:
      8756005