TI  - Heterodimers of <prot>placenta growth factor</prot>/<prot>vascular endothelial growth factor</prot>.
      Endothelial activity, tumor cell expression, and high affinity binding to
      <prot>Flk-1</prot>/<prot>KDR</prot>.
PG  - 3154-62
AB  - Here we show that the Escherichia coli expressed monomers of <prot>placenta
      growth factor</prot> (<prot>PLGF</prot>)129 and <prot>vascular endothelial growth factor</prot> (<prot>VEGF</prot>)165
      can be re-folded in vitro to form  <prot>PLGF</prot> / <prot>VEGF</prot>  heterodimers. The purified
      recombinant  <prot>PLGF</prot> / <prot>VEGF</prot>  heterodimers and   <prot>VEGF</prot>   homodimers have potent
      mitogenic and chemotactic effects on endothelial cells. However,  <prot>PLGF</prot> / <prot>VEGF</prot> 
      heterodimers display 20-50-fold less mitogenic activity than   <prot>VEGF165</prot>  
      homodimers. In contrast,   <prot>PLGF129</prot>   homodimers have little or no effect in
      these in vitro assays. We also demonstrate the presence of natural
       <prot>PLGF</prot> / <prot>VEGF</prot>  heterodimers in the conditioned media of various human tumor
      cell lines. While  <prot>PLGF</prot>/<prot>VEGF</prot>  heterodimers bind with high affinity to a
      soluble  <prot>Flk-1</prot>/<prot><prot>KDR</prot> receptor</prot> ,   <prot>PLGF129</prot>   homodimers fail to bind to this
      receptor. Cross-linking of 125I-ligands to human umbilical vein
      endothelial cells reveals that  <prot>PLGF</prot> / <prot>VEGF</prot>  heterodimers and   <prot>VEGF165</prot>  
      homodimers, but not   <prot>PLGF129</prot>   homodimers, form complexes with membrane
      receptors.   <prot>VEGF165</prot>   homodimers and  <prot>PLGF</prot> / <prot>VEGF</prot>  heterodimers stimulate
      tyrosine phosphorylation of a 220-kDa protein, the expected size for the
      <prot>KDR</prot> receptor in human umbilical vein endothelial cells, whereas   <prot>PLGF129</prot>  
      homodimers are unable to induce tyrosine phosphorylation of this protein.
      These data indicate that <prot>PLGF</prot> may modulate <prot>VEGF</prot>-induced angiogenesis by
      the formation of  <prot>PLGF</prot> / <prot>VEGF</prot>  heterodimers in cells producing both factors.
AD  - Department of Surgery, Harvard Medical School, Boston, Massachusetts
