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Prepublished online as a Blood First Edition Paper on January 23, 2003; DOI 10.1182/blood-2002-10-3227. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3227v1 101/11/4380    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kolev, K. Articles by Machovich, R. Search for Related Content PubMed PubMed Citation Articles by Kolev, K. Articles by Machovich, R. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4380-4386 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Myosin: a noncovalent stabilizer of fibrin in the process of clot dissolution Krasimir Kolev, Kiril Tenekedjiev, Katalin Ajtai, Ilona Kovalszky, Judit Gombás, Balázs Váradi, and Raymund Machovich From the Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary; 1st Department of Pathology, Semmelweis University, Budapest, Hungary; and Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, MN. Myosin modulates the fibrinolytic process as a cofactor of the tissue plasminogen activator and as a substrate of plasmin. We report now that myosin is present in arterial thrombi and it forms reversible noncovalent complexes with fibrinogen and fibrin with equilibrium dissociation constants in the micromolar range (1.70 and 0.94 µM, respectively). Competition studies using a peptide inhibitor of fibrin polymerization (glycl-prolyl-arginyl-proline [GPRP]) indicate that myosin interacts with domains common in fibrinogen and fibrin and this interaction is independent of the GPRP-binding polymerization site in the fibrinogen molecule. An association rate constant of 1.81 x 102 M–1 · s–1 and a dissociation rate constant of 3.07 x 10–4 s–1 are determined for the fibrinogen-myosin interaction. Surface plasmon resonance studies indicate that fibrin serves as a matrix core for myosin aggregation. The fibrin clots equilibrated with myosin are stabilized against dissolution initiated by plasminogen and tissue-type plasminogen activator (tPA) or urokinase (at fibrin monomer-myosin molar ratio as high as 30) and by plasmin under static and flow conditions (at fibrin monomer-myosin molar ratio lower than 15). Myosin exerts similar effects on the tPA-induced dissolution of blood plasma clots. Covalent modification involving factor XIIIa does not contribute to this stabilizing effect; myosin is not covalently attached to the clot by the time of complete cross-linking of fibrin. Thus, our in vitro data suggest that myosin detected in arterial thrombi binds to the polymerized fibrin, in the bound form its tPA-cofactor properties are masked, and the myosinfibrin clot is relatively resistant to plasmin. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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