title: IGFBP-3 proteolysis by plasmin, thrombin, serum: heparin binding, IGF binding, and structure of fragments.
abstract: Insulin-like growth factor binding protein (IGFBP)-3 was exposed to plasmin, thrombin, and pregnancy serum, substances normally present at the endothelial surface in enriched concentrations. The NH2-termini of the proteolytic fragments were sequenced, and their ability to bind insulin-like growth factor (IGF) and heparin was assessed by ligand blotting. Plasmin generated at least five fragments, three beginning at the NH2-terminus of IGFBP-3 and two with NH2-termini corresponding to middle portions of IGFBP-3. The dominant fragment bound both IGF and heparin while NH2-terminal fragments bound only IGF. Thrombin generated three and serum five easily identified fragments; the dominant fragments, beginning at midportions of IGFBP-3, retained IGF and heparin affinity, whereas the remaining fragments had differential affinities for IGF and heparin. We suggest that such fragments, when generated at the endothelia surface, have the potential to alter regional vascular concentrations of IGF and thus influence both IGF and endothelial function.
authors.affiliation: Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, Iowa, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Booth
authors.forename: M
authors.initials: M
authors.lastname: Boes
authors.forename: R S
authors.initials: RS
authors.lastname: Bar
mesh_terms: D001665:Binding Sites; D001769:Blood; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010446:Peptide Fragments; D011247:Pregnancy; D011994:Recombinant Proteins / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D006493:Heparin; D013917:Thrombin; D005341:Fibrinolysin