Cell
Volume 72, Issue 6, 26 March 1993, Pages 835-846
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High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis

https://doi.org/10.1016/0092-8674(93)90573-9Get rights and content

Abstract

Examination of flk-1 receptor tyrosine kinase mRNA expression by in situ hybridization analysis revealed specific association with endothelial cells at all stages of mouse development, including the blood islands in the yolk sac of day 8.5–10.5 embryos, in which the early progenitors of this lineage originate. flk-1 transcripts were abundant in proliferating endothelial cells of vascular sprouts and branching vessels of embryonic and early postnatal brain, but were drastically reduced in adult brain, where proliferation has ceased. Identification of the angiogenic mitogen, vascular endothelial growth factor (VEGF), as the high affinity ligand of Flk-1 and correlation of the temporal and spatial expression pattern of Flk-1 and VEGF suggest a major role of this ligand-receptor signaling system in vasculogenesis and angiogenesis.

References (66)

  • R.M. Kris et al.

    Antibodies against a synthetic peptide as a probe for the kinase activity of the avian EGF receptor and v-erbB protein

    Cell

    (1985)
  • R. Montesano et al.

    Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor

    Cell

    (1991)
  • W. Risau et al.

    Changes in the vascular extracellular matrix during embryonic vasculogenesis and angiogenesis

    Dev. Biol.

    (1988)
  • P.L. Robertson et al.

    Angiogenesis in developing rat brain: an in vivo and in vitro study

    Dev. Brain Res.

    (1985)
  • R. Sarzani et al.

    A novel endothelial tyrosine kinase cDNA homologous to platelet-derived growth factor receptor cDNA

    Biochem. Biophys. Res. Commun.

    (1992)
  • R. Schumacher et al.

    Insulin and insulin-like growth factor-1 binding specificity is determined by distinct regions of their cognate receptors

    J. Biol. Chem.

    (1991)
  • D.B. Smith et al.

    Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase

    Gene

    (1988)
  • A. Ullrich et al.

    Signal transduction by receptors with tyrosine kinase activity

    Cell

    (1990)
  • R.V. Aroian et al.

    The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily

    Nature

    (1990)
  • H. Aviv et al.

    Purification of biologically active globin messenger RNA by chromatography on oligothymidilic acid cellulose

  • T. Bär

    The vascular system of the cerebral cortex

    Adv. Anat. Embryol. Cell. Biol.

    (1980)
  • K. Basler et al.

    Control of photoreceptor cell fate by the sevenless protein requires a functional tyrosine kinase domain

    Cell

    (1988)
  • G. Breier et al.

    Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation

    Development

    (1992)
  • B. Chabot et al.

    The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W-locus

    Nature

    (1988)
  • C. Chen et al.

    High-efficiency transformation of mammalian cells by plasmid DNA

    Mol. Cell. Biol.

    (1987)
  • L. Claesson-Welsh et al.

    cDNA cloning and expression of the human A-type plateletderived growth factor (PDGF) receptor establishes structural similarity to the B-type PDGF receptor

  • M. Clauss et al.

    Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte proagulant activity, and promotes monocyte migration

    J. Exp. Mad.

    (1990)
  • G. Conn et al.

    Purification of a glycoprotein vascular endothelial cell mitogen from a rat glioma-derived cell line

  • C. De Vries et al.

    The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor

    Science

    (1992)
  • C.A. Dionne et al.

    Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors

    EMBO J.

    (1990)
  • D.J. Dumont et al.

    Tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors

    Oncogene

    (1992)
  • R.I. Engermann et al.

    Cell turnover of capillaries

    Lab. Invest.

    (1967)
  • K. Fahmer et al.

    Transcription of H-2 and Qa genes in embryonic and adult mice

    EMBO J.

    (1987)
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    §

    Present address: Department of Molecular Cell Biology, Max Planck Institute for Physiological and Clinical Research, W. G. Kerckhoff Institute, 6350 Bad Nauheim, Germany.

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