Polyphosphate accelerates factor V activation by factor XIa

Sharon H. Choi; Stephanie A. Smith; James H. Morrissey

doi:10.1160/TH14-06-0515

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2015; 113(03): 599-604
DOI: 10.1160/TH14-06-0515

Coagulation and Fibrinolysis

Schattauer GmbH

Polyphosphate accelerates factor V activation by factor XIa

Sharon H. Choi^*

¹Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA

,

Stephanie A. Smith^*

¹Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA

,

James H. Morrissey

¹Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA

› Author Affiliations

Abstract

Summary

Factor Va enhances the rate of prothrombin activation by factor Xa by four to five orders of magnitude. Production of initiating levels of factor Va from its precursor, factor V, is a critical event early in haemostasis, as factor V exhibits negligible cofactor activity. While thrombin is the most potent physiological back-activator of factor V, the first prothrombinase complexes require a source of factor Va prior to thrombin generation. A recent study by Whelihan et al. (J Thromb Haemost 2010; 8:1532–1539) identified factor XIa as a candidate for the initial thrombin-independent activation of factor V, although this reaction was slow and required relatively high concentrations of factors V and XIa. Activated platelets secrete polyphosphate, which we previously showed to be potently procoagulant. We now report that polyphosphate greatly accelerates factor V activation by factor XIa, and that this is supported by polyphosphate polymers of the size secreted by activated human platelets. This finding provides additional evidence that factor XIa-mediated generation of factor Va may contribute to the initiation of haemostasis.

Keywords

Polyphosphate - factor V - factor XI - prothrombinase

Full Text

References

References
1 Esmon CT. The subunit structure of thrombin-activated factor V Isolation of activated factor V, separation of subunits, and reconstitution of biological activity. J Biol Chem 1979; 254: 964-973.
2 Nesheim ME, Myrmel KH, Hibbard L. et al. Isolation and characterization of single chain bovine factor V. J Biol Chem 1979; 254: 508-517.
3 Jenny RJ, Pittman DD, Toole JJ. et al. Complete cDNA and derived amino acid sequence of human factor V. Proc Natl Acad Sci USA 1987; 84: 4846-4850.
4 Monkovic DD, Tracy PB. Activation of human factor V by factor Xa and thrombin. Biochemistry 1990; 29: 1118-1128.
5 Foster WB, Nesheim ME, Mann KG. The factor Xa-catalyzed activation of factor V. J Biol Chem 1983; 258: 13970-13977.
6 Suzuki K, Dahlback B, Stenflo J. Thrombin-catalyzed activation of human coagulation factor V. J Biol Chem 1982; 257: 6556-6564.
7 Owen Jr. CA, Cooper T. Parahemophilia. Arch Intern Med 1955; 95: 194-201.
8 Rosing J, Tans G, Govers-Riemslag JW. et al. The role of phospholipids and factor Va in the prothrombinase complex. J Biol Chem 1980; 255: 274-283.
9 Nesheim ME, Taswell JB, Mann KG. The contribution of bovine factor V and factor Va to the activity of prothrombinase. J Biol Chem 1979; 254: 10952-10962.
10 Kane WH, Majerus PW. Purification and characterization of human coagulation factor V. J Biol Chem 1981; 256: 1002-1007.
11 Bradford HN, Annamalai A, Doshi K. et al. Factor V is activated and cleaved by platelet calpain: comparison with thrombin proteolysis. Blood 1988; 71: 388-394.
12 Samis JA, Garrett M, Manuel RP. et al. Human neutrophil elastase activates human factor V but inactivates thrombin-activated human factor V. Blood 1997; 90: 1065-1074.
13 Camire RM, Kalafatis M, Tracy PB. Proteolysis of factor V by cathepsin G and elastase indicates that cleavage at Arg1545 optimizes cofactor function by facilitating factor Xa binding. Biochemistry 1998; 37: 11896-11906.
14 Safa O, Morrissey JH, Esmon CT. et al. Factor Vila/tissue factor generates a form of factor V with unchanged specific activity, resistance to activation by thrombin, and increased sensitivity to activated protein C. Biochemistry 1999; 38: 1829-1837.
15 Kane WH, Mruk JS, Majerus PW. Activation of coagulation factor V by a platelet protease. J Clin Invest 1982; 70: 1092-1100.
16 Whelihan MF, Orfeo T, Gissel MT. et al. Coagulation procofactor activation by factor XIa. J Thromb Haemost 2010; 8: 1532-1539.
17 Smith SA, Mutch NJ, Baskar D. et al. Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci USA 2006; 103: 903-908.
18 Choi SH, Smith SA, Morrissey JH. Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood 2011; 118: 6963-6970.
19 Smith SA, Choi SH, Davis-Harrison R. et al. Polyphosphate exerts differential effects on blood clotting, depending on polymer size. Blood 2010; 116: 4353-4359.
20 Werner TP, Amrhein N, Freimoser FM. Specific localization of inorganic polyphosphate (poly P) in fungal cell walls by selective extraction and immunohistochemistry. Fungal Genet Biol 2007; 44: 845-852.
21 Morrissey JH. Silver stain for proteins in polyacrylamide gels: a modified procedure with enhanced uniform sensitivity. Anal Biochem 1981; 117: 307-310.
22 Ruiz FA, Lea CR, Oldfield E. et al. Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J Biol Chem 2004; 279: 44250-44257.
23 Müller F, Mutch NJ, Schenk WA. et al. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 2009; 139: 1143-1156.
24 Camire RM. A new look at blood coagulation factor V. Curr Opin Hematol 2011; 18: 338-342.
25 Yang TL, Cui J, Taylor JM. et al. Rescue of fatal neonatal hemorrhage in factor V deficient mice by low level transgene expression. Thromb Haemost 2000; 83: 70-77.
26 Cui J, O’Shea KS, Purkayastha A. et al. Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Nature 1996; 384: 66-68.
27 Keller FG, Ortel TL, Quinn-Allen MA. et al. Thrombin-catalyzed activation of recombinant human factor V. Biochemistry 1995; 34: 4118-4124.
28 Steen M, Dahlback B. Thrombin-mediated proteolysis of factor V resulting in gradual B-domain release and exposure of the factor Xa-binding site. J Biol Chem 2002; 277: 38424-38430.
29 Wood JP, Bunce MW, Maroney SA. et al. Tissue factor pathway inhibitor-alpha inhibits prothrombinase during the initiation of blood coagulation. Proc Natl Acad Sci USA 2013; 110: 17838-17843.
30 Schuijt TJ, Bakhtiari K, Daffre S. et al. Factor Xa activation of factor V is of paramount importance in initiating the coagulation system: lessons from a tick salivary protein. Circulation 2013; 128: 254-266.
31 Talbot K, Song J, Hewitt J. et al. A novel compensating mechanism for homozygous coagulation factor V deficiency suggested by enhanced activated partial thromboplastin time after reconstitution with normal factor V. Br J Haematol 2010; 151: 198-200.
32 Rex S, Beaulieu LM, Perlman DH. et al. Immune versus thrombotic stimulation of platelets differentially regulates signalling pathways, intracellular proteinprotein interactions, and alpha-granule release. Thromb Haemost 2009; 102: 97-110.
33 Mirlashari MR, Ryningen A, Mikkelsen HM. et al. Differential secretion of blood platelet storage granules. Platelets 1996; 7: 313-320