Activation of factor XI by products of prothrombin activation

Anton Matafonov, Suryakala Sarilla, Mao Fu Sun, John P. Sheehan, Vladimir Yurievich Serebrov, Ingrid M. Verhamme, David Gailani

Результат исследований: Материалы для журналаСтатья

38 Цитирования (Scopus)

Аннотация

The prothrombinase complex converts prothrombin to α-thrombin through the intermediate meizothrombin (Mz-IIa). Both α-thrombin and Mz-IIa catalyze factor (F) XI activation to FXIa, which sustains α-thrombin production through activation of FIX. The interaction with FXI is thought to involve thrombin anion binding exosite (ABE) I. α-Thrombin can undergo additional proteolysis to β-thrombin and γ-thrombin, neither of which have an intact ABE I. In a purified protein system, FXI is activated by β-thrombin or γ-thrombin, and by α-thrombin in the presence of the ABE I-blocking peptide hirugen, indicating that a fully formed ABE I is not absolutely required for FXI activation. In a FXI-dependent plasma thrombin generation assay, β-thrombin, γ-thrombin, and α-thrombins with mutations in ABE I are approximately 2-fold more potent initiators of thrombin generation than α-thrombin or Mz-IIa, possibly because fibrinogen, which binds to ABE I, competes poorly with FXI for forms of thrombin lacking ABE I. In addition, FXIa can activate factor FXII, which could contribute to thrombin generation through FXIIa-mediated FXI activation. The data indicate that forms of thrombin other than α-thrombin contribute directly to feedback activation of FXI in plasma and suggest that FXIa may provide a link between tissue factor-initiated coagulation and the proteases of the contact system.

Язык оригиналаАнглийский
Страницы (с-по)437-445
Число страниц9
ЖурналBlood
Том118
Номер выпуска2
DOI
СостояниеОпубликовано - 14 июл 2011
Опубликовано для внешнего пользованияДа

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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  • Цитировать

    Matafonov, A., Sarilla, S., Sun, M. F., Sheehan, J. P., Serebrov, V. Y., Verhamme, I. M., & Gailani, D. (2011). Activation of factor XI by products of prothrombin activation. Blood, 118(2), 437-445. https://doi.org/10.1182/blood-2010-10-312983