Localization of a Vitronectin Binding Region of Plasminogen Activator Inhibitor-1

Jaya Padmanabhan; David C Sane

doi:10.1055/s-0038-1653876

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1995; 73(05): 829-834
DOI: 10.1055/s-0038-1653876

Original Articles

Fibrinolysis

Schattauer GmbH Stuttgart

Localization of a Vitronectin Binding Region of Plasminogen Activator Inhibitor-1

Jaya Padmanabhan

²The Department of Internal Medicine, The Bowman Gray School of Medicine, Winston-Salem, NC, USA

,

David C Sane

²The Department of Internal Medicine, The Bowman Gray School of Medicine, Winston-Salem, NC, USA

› Author Affiliations

Abstract

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Summary

The PAI-1 binding site for VN was studied using two independent methods. PAI-1 was cleaved by Staph V8 protease, producing 8 fragments, only 2 of which bound to [¹²⁵I]-VN. These fragments were predicted to overlap between residues 91-130. Since PAI-2 has structural homology to PAI-1, but does not bind to vitronectin, chimeras of PAI-1 and PAI-2 were constructed. Four chimeras, containing PAI-1 residues 1-70,1-105,1-114, and 1-167 were constructed and expressed in vitro. PAI-1, PAI-2, and all of the chimeras retained inhibitory activity for t-PA, but only the chimera containing PAI-1 residues 1-167 formed a complex with VN. Together, these results predict that the VN binding site of PAI-1 is between residues 115-130.

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References

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