Proteolytic cleavage of protein S during the hemostatic response.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: England NLM ID: 101170508 Publication Model: Print Cited Medium: Print ISSN: 1538-7933 (Print) Linking ISSN: 15387836 NLM ISO Abbreviation: J Thromb Haemost Subsets: MEDLINE
    • Publication Information:
      Publication: 2023- : [New York] : Elsevier
      Original Publication: Oxford : Blackwell Pub.
    • Subject Terms:
      Hemostasis*; Factor Xa/*metabolism ; Protein S/*metabolism ; Thrombin/*metabolism; Binding Sites ; Blood Coagulation ; Blood Platelets/cytology ; Blood Platelets/physiology ; Cells, Cultured ; Endothelium, Vascular/cytology ; Humans ; Kinetics ; Liposomes/pharmacology ; Protein S/physiology
    • Abstract:
      Background: Protein S is a vitamin K-dependent protein with anticoagulant properties. It contains a so-called thrombin-sensitive region (TSR), which is susceptible to cleavage by coagulation factor Xa (FXa) and thrombin. Upon cleavage, the anticoagulant activity of protein S is abolished.
      Objective: The aim of the present study was to determine whether protein S is cleaved within the TSR during activation of the coagulation system under near physiological conditions.
      Results: In a reconstituted coagulation system containing apart from protein S only procoagulant constituents and synthetic phospholipid vesicles, protein S was cleaved at Arg60 by the FXa generated (3 mol min(-1) mol(-1) enzyme). FXa-catalyzed cleavage of protein S, however, was inhibited by factor Va and prothrombin by more than 70%. During clotting of recalcified citrated plasma in the presence of a synthetic lipid membrane, no FXa-catalyzed proteolysis of protein S was observed. Substituting platelets for phospholipid vesicles resulted both in the reconstituted system and in plasma in cleavage of the TSR. Cleavage was at Arg60 and was observed upon platelet activation, irrespective of the presence of FXa (13 pmol min(-1) 10(-8) platelets). No cleavage by thrombin was observed in either the reconstituted coagulation system or clotting plasma.
      Conclusion: These findings suggest that in vivo the anticoagulant activity of protein S is not down-regulated by FXa or thrombin during activation of coagulation. Our results rather suggest a role for a platelet protease in down-regulating the anticoagulant activity of protein S during the hemostatic response.
    • Accession Number:
      0 (Liposomes)
      0 (Protein S)
      EC 3.4.21.5 (Thrombin)
      EC 3.4.21.6 (Factor Xa)
    • Publication Date:
      Date Created: 20051220 Date Completed: 20060221 Latest Revision: 20230829
    • Publication Date:
      20231215
    • Accession Number:
      10.1111/j.1538-7836.2005.01647.x
    • Accession Number:
      16359509