The roles of factor Va and protein S in formation of the activated protein C/protein S/factor Va inactivation complex.

Journal of Thrombosis and Haemostasis : JTH
Magdalena GierulaJosefin Ahnström

Abstract

Activated protein C (APC)-mediated inactivation of factor (F)Va is greatly enhanced by protein S. For inactivation to occur, a trimolecular complex among FVa, APC, and protein S must form on the phospholipid membrane. However, direct demonstration of complex formation has proven elusive. To elucidate the nature of the phospholipid-dependent interactions among APC, protein S, and FVa. We evaluated binding of active site blocked APC to phospholipid-coated magnetic beads in the presence and absence of protein S and/or FVa. The importance of protein S and FV residues were evaluated functionally. Activated protein C alone bound weakly to phospholipids. Protein S mildly enhanced APC binding to phospholipid surfaces, whereas FVa did not. However, FVa together with protein S enhanced APC binding (>14-fold), demonstrating formation of an APC/protein S/FVa complex. C4b binding protein-bound protein S failed to enhance APC binding, agreeing with its reduced APC cofactor function. Protein S variants (E36A and D95A) with reduced APC cofactor function exhibited essentially normal augmentation of APC binding to phospholipids, but diminished APC/protein S/FVa complex formation, suggesting involvement in interactions dependent upon FVa. Similar...Continue Reading

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Citations

Jul 24, 2020·Journal of Thrombosis and Haemostasis : JTH·Magdalena Gierula, Josefin Ahnström
Jan 7, 2021·Journal of Thrombosis and Haemostasis : JTH·Herm Jan M BrinkmanRichard A Marlar
Jan 9, 2021·International Journal of Hematology·Masahiro IekoDongchon Kang
Feb 20, 2021·Journal of Thrombosis and Haemostasis : JTH·Elisabetta CastoldiPierre-Emmanuel Morange
Apr 22, 2021·Journal of Thrombosis and Haemostasis : JTH·Josefin Ahnström, Gary E Gilbert

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Methods Mentioned

BETA
flow cytometry
flow

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