Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR.

作者: John E Park , Helen H Chen , Jane Winer , Keith A Houck , Napoleone Ferrara

DOI: 10.1016/S0021-9258(18)47298-5

关键词:

摘要: The recently identified placenta growth factor (PIGF) is a member of the vascular endothelial (VEGF) family factors. PIGF displays 53% identity with platelet-derived factor-like region VEGF. By alternative splicing RNA, two isoforms are generated: PIGF131 (PIGF-1) and PIGF152 (PIGF-2). Relative to PIGF131, has 21-amino acid insertion enriched in basic amino acids. Little known at present time about significance function these proteins. To assess their potential role, we cloned cDNAs coding for both isoforms, expressed them mammalian cells, purified apparent homogeneity recombinant Like VEGF, homodimeric glycoproteins. non-heparin binding protein, whereas strongly binds heparin. We examined ability bind soluble VEGF receptors, Flt-1 Flk-1/KDR, characterized cells. While proteins bound high affinity Flt-1, they failed Flk-1/KDR. Binding 125I-PIGF human cells revealed classes sites, having low affinity. site consistent Flt-1; remains be determined. Purified had little or no direct mitogenic permeability-enhancing activity. However, were able significantly potentiate action concentrations vitro and, more strikingly, vivo.

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