[Molecular biology of protein C-thrombomodulin pathway. Structure and function, and basic studies on its clinical application].
Vascular endothelial cells have several mechanisms which play an active role in preventing blood clot formation in vivo. One of the mechanisms by which prevention is achieved involves a cell surface thrombin receptor, thrombomodulin, which converts thrombin from a procoagulant into an anticoagulant due to accelerating thrombin-catalyzed activation of an anticoagulant protease zymogen, protein C. Activated protein C then proteolytically inactivates coagulation cofactors, Factors Va and VIIIa, in concert with another anticoagulant protein S. Activated protein C is finally neutralized by protein C inhibitor. The physiological relevance of the anticoagulant protein C-thrombomodulin pathway is demonstrated by the identification of hereditary deficiency of protein C or protein S with severe thrombotic complications. The recombinant protein C or thrombomodulin would be useful for treatment of the thrombotic diseases.
Department of Molecular Biology on Genetic Disease, Mie University School of Medicine.
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Hayashi
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Suzuki
D000595:Amino Acid Sequence; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D011486:Protein C / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000502:physiology*; D018179:Receptors, Thrombin; D013917:Thrombin / Q000378:metabolism*
D005343:Fibrinolytic Agents; D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D013917:Thrombin