Limited Proteolysis of Vitronectin by Plasmin Destroys Heparin Binding Activity

David C Sane; Tammy L Moser; Charles S Greenberg

doi:10.1055/s-0038-1646413

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1991; 66(03): 310-314
DOI: 10.1055/s-0038-1646413

Review Article

Schattauer GmbH Stuttgart

Limited Proteolysis of Vitronectin by Plasmin Destroys Heparin Binding Activity

David C Sane

^*The Department of Medicine, Duke University Medical Center, Durham, NC, USA

,

Tammy L Moser

^*The Department of Medicine, Duke University Medical Center, Durham, NC, USA

,

Charles S Greenberg

^**The Department of Pathology, Duke University Medical Center, Durham, NC, USA

› Author Affiliations

Abstract

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Summary

Vitronectin (VN) stabilizes plasminogen activator inhibitor type 1 (PAI-1) activity and prevents the fibrin(ogen)-induced acceleration of plasminogen activation by t-PA. These antifibrinolytic activities as well as other functions are mediated by the glycosaminoglycan (GAG) binding domain of VN. Since the GAG binding region is rich in arginyl and lysyl residues, it is a potential target for enzymes such as plasmin. In this paper, the dose and time-dependent proteolysis of VN by plasmin is demonstrated. The addition of urokinase or streptokinase (200 units/ml) to plasma also produced proteolysis of VN. With minimal proteolysis, the 75 kDa band was degraded to a 62-65 kDa form of VN. This minimal proteolysis destroyed the binding of [³H]-heparin to VN and reversed the neutralization of heparin by VN.

Thus, the plasmin-mediated proteolysis of the GAG binding activity of VN could destroy the antifibrinolytic activity of VN during physiologic conditions and during thrombolytic therapy. Furthermore, other functions of VN in complement and coagulation systems that are mediated by the GAG binding domain may be destroyed by plasmin proteolysis.

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References

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