Novel APC-cleavage sites in FVa provide insights into mechanisms of action of APC and its cofactor protein S

Journal of Thrombosis and Haemostasis

Volumn 8, Issue 1, 2010, Pages 129-136

  Tran, S ^a   Dahlbank, B ^a  

^a LUND UNIVERSITY   (Sweden)

Author keywords

Activated protein C; APC resistance; Factor V; FV Leiden; Protein C; Protein S

Indexed keywords

ACTIVATED PROTEIN C; ARGININE; BLOOD CLOTTING FACTOR 5A; COMPLEMENTARY DNA; LYSINE; PROTEIN S;

ARTICLE; CONTROLLED STUDY; DEGRADATION KINETICS; ENZYME ACTIVE SITE; ENZYME DEGRADATION; GENE MUTATION; PRIORITY JOURNAL; PROTEIN FUNCTION;

AMINO ACID SEQUENCE; ARGININE; FACTOR VA; HUMANS; KINETICS; LYSINE; MUTAGENESIS, SITE-DIRECTED; MUTATION; PHOSPHOLIPIDS; PROTEIN C; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN S; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 73049099489     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2009.03657.x     Document Type: Article

References (32)

1. Dahlbäck B. Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis of bleeding and thrombotic diseases. J Intern Med 2005, 257:209-23.
2. Butenas S, Mann KG. Blood coagulation. Biochemistry (Mosc) 2002, 67:3-12.
3. Segers K, Dahlbäck B, Nicolaes GA. Coagulation factor V and thrombophilia: background and mechanisms. Thromb Haemost 2007, 98:530-42.
4. Esmon CT, Ding W, Yasuhiro K, Gu JM, Ferrell G, Regan LM, Stearns-Kurosawa DJ, Kurosawa S, Mather T, Laszik Z, Esmon NL. The protein C pathway: new insights. Thromb Haemost 1997, 78:70-4.
5. Kalafatis M, Rand MD, Mann KG. The mechanism of inactivation of human factor V and human factor Va by activated protein C. J Biol Chem 1994, 269:31869-80.
6. Nicolaes GA, Tans G, Thomassen MC, Hemker HC, Pabinger I, Varadi K, Schwarz HP, Rosing J. Peptide bond cleavages and loss of functional activity during inactivation of factor Va and factor VaR506Q by activated protein C. J Biol Chem 1995, 270:21158-66.
7. Mann KG, Hockin MF, Begin KJ, Kalafatis M. Activated protein C cleavage of factor Va leads to dissociation of the A2 domain. J Biol Chem 1997, 272:20678-83.
8. Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A 1993, 90:1004-8.
9. Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994, 369:64-7.
10. Chan WP, Lee CK, Kwong YL, Lam CK, Liang R. A novel mutation of Arg306 of factor V gene in Hong Kong Chinese. Blood 1998, 91:1135-9.
11. Williamson D, Brown K, Luddington R, Baglin C, Baglin T. Factor V Cambridge: a new mutation (Arg306-->Thr) associated with resistance to activated protein C. Blood 1998, 91:1140-4.
12. Walker FJ. Regulation of activated protein C by a new protein. A possible function for bovine protein S. J Biol Chem 1980, 255:5521-4.
13. Castoldi E, Hackeng TM. Regulation of coagulation by protein S. Curr Opin Hematol 2008, 15:529-36.
14. Dahlbäck B. The tale of protein S and C4b-binding protein, a story of affection. Thromb Haemost 2007, 98:90-6.
15. Garcia de Frutos P, Fuentes-Prior P, Hurtado B, Sala N. Molecular basis of protein S deficiency. Thromb Haemost 2007, 98:543-56.
16. Rosing J, Hoekema L, Nicolaes GA, Thomassen MC, Hemker HC, Varadi K, Schwarz HP, Tans G. Effects of protein S and factor Xa on peptide bond cleavages during inactivation of factor Va and factor VaR506Q by activated protein C. J Biol Chem 1995, 270:27852-8.
17. Norstrøm EA, Steen M, Tran S, Dahlbäck B. Importance of protein S and phospholipid for activated protein C-mediated cleavages in factor Va. J Biol Chem 2003, 278:24904-11.
18. Norstrøm EA, Tran S, Steen M, Dahlbäck B. Effects of factor Xa and protein S on the individual activated protein C-mediated cleavages of coagulation factor Va. J Biol Chem 2006, 281:31486-94.
19. Yegneswaran S, Smirnov MD, Safa O, Esmon NL, Esmon CT, Johnson AE. Relocating the active site of activated protein C eliminates the need for its protein S cofactor. A fluorescence resonance energy transfer study. J Biol Chem 1999, 274:5462-8.
20. Friedrich U, Nicolaes GA, Villoutreix BO, Dahlbäck B. Secondary substrate-binding exosite in the serine protease domain of activated protein C important for cleavage at Arg-506 but not at Arg-306 in factor Va. J Biol Chem 2001, 276:23105-8.
21. Gale AJ, Tsavaler A, Griffin JH. Molecular characterization of an extended binding site for coagulation factor Va in the positive exosite of activated protein C. J Biol Chem 2002, 277:28836-40.
22. van der Neut Kolfschoten M, Dirven RJ, Vos HL, Tans G, Rosing J, Bertina RM. Factor Va is inactivated by activated protein C in the absence of cleavage sites at Arg-306, Arg-506, and Arg-679. J Biol Chem 2004, 279:6567-75.
23. Sun YH, Shen L, Dahlbäck B. Gla domain-mutated human protein C exhibiting enhanced anticoagulant activity and increased phospholipid binding. Blood 2003, 101:2277-84.
24. Friedrich U, Blom AM, Dahlbäck B, Villoutreix BO. Structural and energetic characteristics of the heparin-binding site in antithrombotic protein C. J Biol Chem 2001, 276:24122-8.
25. Dahlbäck B, Wiedmer T, Sims PJ. Binding of anticoagulant vitamin K-dependent protein S to platelet-derived microparticles. Biochemistry. 1992, 31:12769-77.
26. Thorelli E, Kaufman RJ, Dahlbäck B. Cleavage of factor V at Arg 506 by activated protein C and the expression of anticoagulant activity of factor V. Blood 1999, 93:2552-8.
27. Norstrøm E, Thorelli E, Dahlbäck B. Functional characterization of recombinant FV Hong Kong and FV Cambridge. Blood 2002, 100:524-30.
28. Sun YH, Tran S, Norstrøm EA, Dahlbäck B. Enhanced rate of cleavage at Arg-306 and Arg-506 in coagulation factor Va by Gla domain-mutated human-activated protein C. J Biol Chem 2004, 279:47528-35.
29. Tran S, Norstrøm E, Dahlbäck B. Effects of prothrombin on the individual activated protein C-mediated cleavages of coagulation factor Va. J Biol Chem 2008, 283:6648-55.
30. MacDonald RC, MacDonald RI, Menco BP, Takeshita K, Subbarao NK, Hu LR. Small-volume extrusion apparatus for preparation of large, unilamellar vesicles. Biochim Biophys Acta 1991, 1061:297-303.
31. Mann KG, Kalafatis M. Factor V: a combination of Dr Jekyll and Mr Hyde. Blood 2003, 101:20-30.
32. Erdogan E, Bukys MA, Orfeo T, Mann KG, Kalafatis M. Identification of an inactivating cleavage site for alpha-thrombin on the heavy chain of factor Va. Thromb Haemost 2007, 98:998-1006.