title: IGFBP-3 binding to endothelial cells inhibits plasmin and thrombin proteolysis.
abstract: Insulin-like growth factor-binding protein (IGFBP)-3 contains a highly basic COOH-terminal heparin-binding region, the P3 region, which is thought to be important in the binding of IGFBP-3 to endothelial cells. IGFBP-3 and IGFBP-4, and their chimeras IGFBP-3(4) and IGFBP-4(3), were treated with plasmin and with thrombin, proteases known to cleave IGFBP-3. IGFBP-3 was highly susceptible to plasmin, whereas IGFBP-4 was less so. Substitution of the P3 region for the P4 region in IGFBP-4 (IGFBP-4(3)) increased the ability of the protease to digest IGFBP-4(3); substitution of the P4 region for the P3 region in IGFBP-3 (IGFBP-3(4)) decreased the digestion of IGFBP-3(4). When 125I-labeled IGFBP-3 or 125I-IGFBP-4(3) was first bound to vascular endothelial cells, subsequent proteolysis by either plasmin or thrombin was substantially inhibited. Proteolysis of 125I-IGFBP-3(4) was not inhibited in the presence of endothelial cells. The P3 peptide was cleaved by plasmin but not by thrombin. We conclude that the P3 region is central to proteolysis of IGFBP-3 by plasmin and thrombin, processes which were inhibited by association of IGFBP-3 with endothelial cells.
authors.affiliation: Department of Internal Medicine, Diabetes and Endocrinology Research Center, Veterans Administration Medical Center, The University of Iowa, Iowa City, IA 52246, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Booth
authors.forename: M
authors.initials: M
authors.lastname: Boes
authors.forename: B L
authors.initials: BL
authors.lastname: Dake
authors.forename: K L
authors.initials: KL
authors.lastname: Knudtson
authors.forename: R S
authors.initials: RS
authors.lastname: Bar
mesh_terms: D000818:Animals; D002417:Cattle; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000737:chemistry / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D013917:Thrombin / Q000378:metabolism*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D010447:Peptide Hydrolases; D013917:Thrombin; D005341:Fibrinolysin