IGFBP-3 binding to endothelial cells inhibits plasmin and thrombin proteolysis

B A Booth; M Boes; B L Dake; K L Knudtson; R S Bar

doi:10.1152/ajpendo.2002.282.1.e52

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IGFBP-3 binding to endothelial cells inhibits plasmin and thrombin proteolysis

Journal article

Peer reviewed

IGFBP-3 binding to endothelial cells inhibits plasmin and thrombin proteolysis

B A Booth, M Boes, B L Dake, K L Knudtson and R S Bar

American journal of physiology: endocrinology and metabolism, Vol.282(1), pp.E52-E58

01/2002

DOI: 10.1152/ajpendo.2002.282.1.e52

PMID: 11739083

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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.

Animals

Cattle

Endothelium, Vascular - cytology

Endothelium, Vascular - metabolism

Fibrinolysin - metabolism

Insulin-Like Growth Factor Binding Protein 3 - chemistry

Insulin-Like Growth Factor Binding Protein 3 - metabolism

Peptide Hydrolases - metabolism

Protein Structure, Tertiary - physiology

Thrombin - metabolism

Details

Title: Subtitle: IGFBP-3 binding to endothelial cells inhibits plasmin and thrombin proteolysis
Creators: B A Booth - Iowa Diabetes and Endocrinology Research Center
M Boes - Iowa Diabetes and Endocrinology Research Center
B L Dake - University of Iowa
K L Knudtson - Iowa Diabetes and Endocrinology Research Center
R S Bar - University of Iowa
Resource Type: Journal article
Publication Details: American journal of physiology: endocrinology and metabolism, Vol.282(1), pp.E52-E58
DOI: 10.1152/ajpendo.2002.282.1.e52
PMID: 11739083
ISSN: 0193-1849
eISSN: 1522-1555
Grant note: DK-25295 / NIDDK NIH HHS DK-25421 / NIDDK NIH HHS
Language: English
Date published: 01/2002
Academic Unit: Endocrinology and Metabolism; Internal Medicine; Iowa Institute of Human Genetics
Record Identifier: 9984627319302771

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