Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Mar;80(6):1584–1588. doi: 10.1073/pnas.80.6.1584

Human coagulation factor Va is a cofactor for the activation of protein C.

H H Salem, G J Broze, J P Miletich, P W Majerus
PMCID: PMC393646  PMID: 6572921

Abstract

During blood clotting in vitro, protein C is converted in part to protein Ca, Protein Ca, in turn, inactivates factor Va. This is evidenced by the rapid inactivation of factor Va coagulant activity after clot formation which is associated with the cleavage of the Mr 110,000 peptide of factor Va. When exogenous factor Va is added to serum, it is inactivated only after a lag of 10-20 min. Using purified coagulation factors in the presence of EDTA, we demonstrated that factor Va enhances the rate of protein C activation by thrombin by 50-fold. The Km for factor Va in the reaction is 14 nM, 100 times higher than its Km for accelerating platelet surface prothrombin activation by factor Xa. By this mechanism, factor Va can act as a procoagulant as well as limit dissemination of the coagulation process through the activation of protein C and the subsequent inactivation of both factor Va and factor VIIIa.

Full text

PDF
1584

Images in this article

1585Image
on p.1585

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Coots M. C., Muhleman A. F., Glueck H. I. Hemorrhagic death associated with a high titer factor V inhibitor. Am J Hematol. 1978;4(2):193–206. doi: 10.1002/ajh.2830040212. [DOI] [PubMed] [Google Scholar]
  2. Esmon C. T., Owen W. G. Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2249–2252. doi: 10.1073/pnas.78.4.2249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Esmon C. T., Stenflo J., Suttie J. W. A new vitamin K-dependent protein. A phospholipid-binding zymogen of a serine esterase. J Biol Chem. 1976 May 25;251(10):3052–3056. [PubMed] [Google Scholar]
  4. Esmon N. L., Owen W. G., Esmon C. T. Isolation of a membrane-bound cofactor for thrombin-catalyzed activation of protein C. J Biol Chem. 1982 Jan 25;257(2):859–864. [PubMed] [Google Scholar]
  5. Griffin J. H., Evatt B., Zimmerman T. S., Kleiss A. J., Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest. 1981 Nov;68(5):1370–1373. doi: 10.1172/JCI110385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Jackson C. M., Nemerson Y. Blood coagulation. Annu Rev Biochem. 1980;49:765–811. doi: 10.1146/annurev.bi.49.070180.004001. [DOI] [PubMed] [Google Scholar]
  7. Kane W. H., Majerus P. W. Purification and characterization of human coagulation factor V. J Biol Chem. 1981 Jan 25;256(2):1002–1007. [PubMed] [Google Scholar]
  8. Kane W. H., Majerus P. W. The interaction of human coagulation factor Va with platelets. J Biol Chem. 1982 Apr 10;257(7):3963–3969. [PubMed] [Google Scholar]
  9. Kisiel W., Ericsson L. H., Davie E. W. Proteolytic activation of protein C from bovine plasma. Biochemistry. 1976 Nov 2;15(22):4893–4900. doi: 10.1021/bi00667a022. [DOI] [PubMed] [Google Scholar]
  10. Kisiel W. Human plasma protein C: isolation, characterization, and mechanism of activation by alpha-thrombin. J Clin Invest. 1979 Sep;64(3):761–769. doi: 10.1172/JCI109521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  12. Marlar R. A., Griffin J. H. Deficiency of protein C inhibitor in combined factor V/VIII deficiency disease. J Clin Invest. 1980 Nov;66(5):1186–1189. doi: 10.1172/JCI109952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Miletich J. P., Broze G. J., Jr, Majerus P. W. The synthesis of sulfated dextran beads for isolation of human plasma coagulation factors II, IX, and X. Anal Biochem. 1980 Jul 1;105(2):304–310. doi: 10.1016/0003-2697(80)90462-5. [DOI] [PubMed] [Google Scholar]
  14. Miletich J. P., Jackson C. M., Majerus P. W. Interaction of coagulation factor Xa with human platelets. Proc Natl Acad Sci U S A. 1977 Sep;74(9):4033–4036. doi: 10.1073/pnas.74.9.4033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Miletich J. P., Kane W. H., Hofmann S. L., Stanford N., Majerus P. W. Deficiency of factor Xa-factor Va binding sites on the platelets of a patient with a bleeding disorder. Blood. 1979 Nov;54(5):1015–1022. [PubMed] [Google Scholar]
  16. Miletich J. P., Majerus D. W., Majerus P. W. Patients with congenital factor V deficiency have decreased factor Xa binding sites on their platelets. J Clin Invest. 1978 Oct;62(4):824–831. doi: 10.1172/JCI109194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Owen W. G., Esmon C. T. Functional properties of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. J Biol Chem. 1981 Jun 10;256(11):5532–5535. [PubMed] [Google Scholar]
  18. Stenflo J. A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization. J Biol Chem. 1976 Jan 25;251(2):355–363. [PubMed] [Google Scholar]
  19. Suzuki K., Dahlbäck B., Stenflo J. Thrombin-catalyzed activation of human coagulation factor V. J Biol Chem. 1982 Jun 10;257(11):6556–6564. [PubMed] [Google Scholar]
  20. Suzuki K., Stenflo J., Dahlbäck B., Teodorsson B. Inactivation of human coagulation factor V by activated protein C. J Biol Chem. 1983 Feb 10;258(3):1914–1920. [PubMed] [Google Scholar]
  21. Vehar G. A., Davie E. W. Preparation and properties of bovine factor VIII (antihemophilic factor). Biochemistry. 1980 Feb 5;19(3):401–410. doi: 10.1021/bi00544a001. [DOI] [PubMed] [Google Scholar]
  22. Walker F. J., Sexton P. W., Esmon C. T. The inhibition of blood coagulation by activated Protein C through the selective inactivation of activated Factor V. Biochim Biophys Acta. 1979 Dec 7;571(2):333–342. doi: 10.1016/0005-2744(79)90103-7. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES