IGFBP-3 PROTEOLYSIS BY PLASMIN, THROMBIN, SERUM - HEPARIN-BINDING, IGF BINDING, AND STRUCTURE OF FRAGMENTS

IGFBP-3 proteolysis by plasmin, thrombin, serum: heparin binding, IGF binding, and structure of fragments. Am. J. Physiol. 271 (Endocrinol. Metab. 34): E465-E470, 1996.-Insulin-like growth factor binding protei n (IGFBP)-3 was exposed to plasmin, thrombin, and pregnancy serum, sub stances normally present at the endothelial surface in enriched concen trations. The NH2-termini of the proteolytic fragments were sequenced, and their ability to bind insulin-like growth factor (IGF) and hepari n was assessed by ligand blotting. Plasmin generated at least five fra gments, three beginning at the NH2-terminus of IGFBP-3 and two with NH 2-termini corresponding to middle portions of IGFBP-3. The dominant fr agment bound both IGF and heparin while NH2-terminal fragments bound o nly IGF. Thrombin generated three and serum five easily identified fra gments; the dominant fragments, beginning at midportions of IGFBP-3, r etained IGF and heparin affinity, whereas the remaining fragments had differential affinities for IGF and heparin. We suggest that such frag ments, when generated at the endothelial surface, have the potential t o alter regional vascular concentrations of IGF and thus influence bot h IGF and endothelial function.