TI  -  <prot><prot>Vascular endothelial growth factor</prot>-related protein</prot> : a ligand and specific
      activator of the tyrosine kinase receptor  <prot>Flt4</prot> .
PG  - 1988-92
AB  - The tyrosine kinases <prot>Flt4</prot>, <prot>Flt1</prot>, and <prot>Flk1</prot> (or <prot>KDR</prot>) constitute a family of
      endothelial cell-specific receptors with seven immunoglobulin-like domains
      and a split kinase domain.  <prot>Flt1</prot>  and  <prot>Flk1</prot>  have been shown to play key roles
      in vascular development; these two receptors bind and are activated by
        <prot>vascular endothelial growth factor</prot> (<prot>VEGF</prot>)  . No ligand has been identified
      for <prot>Flt4</prot>, whose expression becomes restricted during development to the
      lymphatic endothelium. We have identified cDNA clones from a human glioma
      cell line that encode a secreted protein with 32% amino acid identity to
      <prot>VEGF</prot>. This protein, designated  <prot><prot>VEGF</prot>-related protein</prot> (<prot>VRP</prot>) , specifically
      binds to the extracellular domain of  <prot>Flt4</prot> , stimulates the tyrosine
      phosphorylation of <prot>Flt4</prot> expressed in mammalian cells, and promotes the
      mitogenesis of human lung endothelial cells. <prot>VRP</prot> fails to bind appreciably
      to the extracellular domain of <prot>Flt1</prot> or <prot>Flk1</prot>. The protein contains a
      C-terminal, cysteine-rich region of about 180 amino acids that is not
      found in <prot>VEGF</prot>. A 2.4-kb VRP mRNA is found in several human tissues
      including adult heart, placenta, ovary, and small intestine and in fetal
      lung and kidney.
AD  - Department of Molecular Biology, Genetech, Inc., South San Francisco, CA
