The Gla26 Residue of Protein C Is Required for the Binding of Protein C to Thrombomodulin and Endothelial Cell Protein C Receptor, but not to Protein S and Factor Va

Junji Nishioka; Masaru Ido; Tatsuya Hayashi; Koji Suzuki

doi:10.1055/s-0038-1650260

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 75(02): 275-282
DOI: 10.1055/s-0038-1650260

Original Article

Schattauer GmbH Stuttgart

The Gla²⁶ Residue of Protein C Is Required for the Binding of Protein C to Thrombomodulin and Endothelial Cell Protein C Receptor, but not to Protein S and Factor Va

Authors

Junji Nishioka

The Department of Molecular Pathobiology, Mie University School of Medicine, Mie, Japan
Masaru Ido

The Department of Molecular Pathobiology, Mie University School of Medicine, Mie, Japan
Tatsuya Hayashi

The Department of Molecular Pathobiology, Mie University School of Medicine, Mie, Japan
Koji Suzuki

The Department of Molecular Pathobiology, Mie University School of Medicine, Mie, Japan

Abstract

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Summary

A functionally defective protein C (PC)-Mie, detected in the plasma of a patient with hereditary thrombophilia, has Lys substituted for γ-carboxyglutamic acid (Gla)²⁶ residue. The activation rate of PC-Mie by Protac or thrombin in the absence of Ca²⁺ and that by thrombin with native thrombomodulin (TM), recombinant soluble truncated TM or on cultured endothelial cells in the presence of Ca²⁺ were all apparently lower than that of normal PC. The anticoagulant activity of Protac-activated PC (APC)-Mie on the plasma clotting time and the rate of inactivation of factor Va by APC-Mie in the presence of phospholipids were lower than those seen with normal APC. APC-Mie and normal APC bound equally to protein S and to biotinyl-factor Va. However, neither PC-Mie nor APC-Mie bound to phospholipids and to cultured human endothelial cells. It was similar to that observed with Gla-domainless PC/APC, but different from that seen with normal PC/APC. These results suggest that Gla²⁶-dependent conformation is required for the binding of PC/APC to phospholipids, TM and the surface of endothelial cell PC/APC receptor, but not to protein S and factor Va.

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References

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