Download PDF
Thromb Haemost 1991; 66(03): 310-314
DOI: 10.1055/s-0038-1646413
Review Article
Schattauer GmbH Stuttgart

Limited Proteolysis of Vitronectin by Plasmin Destroys Heparin Binding Activity

David C Sane
*   The Department of Medicine, Duke University Medical Center, Durham, NC, USA
,
Tammy L Moser
*   The Department of Medicine, Duke University Medical Center, Durham, NC, USA
,
Charles S Greenberg
**   The Department of Pathology, Duke University Medical Center, Durham, NC, USA
› Author Affiliations
Further Information

Publication History

Received 06 September 1990

Accepted 11 March 1991

Publication Date:
25 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Vitronectin (VN) stabilizes plasminogen activator inhibitor type 1 (PAI-1) activity and prevents the fibrin(ogen)-induced acceleration of plasminogen activation by t-PA. These antifibrinolytic activities as well as other functions are mediated by the glycosaminoglycan (GAG) binding domain of VN. Since the GAG binding region is rich in arginyl and lysyl residues, it is a potential target for enzymes such as plasmin. In this paper, the dose and time-dependent proteolysis of VN by plasmin is demonstrated. The addition of urokinase or streptokinase (200 units/ml) to plasma also produced proteolysis of VN. With minimal proteolysis, the 75 kDa band was degraded to a 62-65 kDa form of VN. This minimal proteolysis destroyed the binding of [3H]-heparin to VN and reversed the neutralization of heparin by VN.

Thus, the plasmin-mediated proteolysis of the GAG binding activity of VN could destroy the antifibrinolytic activity of VN during physiologic conditions and during thrombolytic therapy. Furthermore, other functions of VN in complement and coagulation systems that are mediated by the GAG binding domain may be destroyed by plasmin proteolysis.

 

  • References

  • 1 Preissner KT. The role of vitronectin as multifunctional regulator in the hemostatic and immune systems. Blut 1989; 59: 419-31
    CrossrefPubMedGoogle Scholar
  • 2 Declerck PJ, De Mol M, Alessi M-C, Baudner S, Pòques EP, Preissner KT, Müller-Berghaus G, Collen D. Purification and characterization of a plasminogen activator inhibitor binding protein from human plasma. J Biol Chem 1988; 263: 15454-61
    PubMedGoogle Scholar
  • 3 Mimuro J, Loskutoff DJ. Purification of a protein from bovine plasma that binds to type 1 plasminogen activator inhibitor and prevents its interaction with extracellular matrix. J Biol Chem 1989; 264: 936-9
    PubMedGoogle Scholar
  • 4 Wiman B, Almqvist Å, Sigurdardottir O, Lindahl T. Plasminogen activator inhibitor (PAI) is bound to vitronectin in plasma. FEBS Lett 1988; 242: 125-8
    CrossrefPubMedGoogle Scholar
  • 5 Salonen EM, Vaheri A, Pollanen J, Stephens R, Andreasen P, Mayer M, Dano K, Gailet J, Ruoslahti E. Interaction of plasminogen activator inhibitor (PAI-1) with vitronectin. J Biol Chem 1989; 264: 6339-43
    PubMedGoogle Scholar
  • 6 Preissner KT. Specific binding of plasminogen to vitronectin. Evidence for a modulatory role of vitronectin on fibrin(ogen)-induced plasmin formation by tissue plasminogen activator. Biochem Biophys Res Commun 1990; 168: 966-71
    CrossrefPubMedGoogle Scholar
  • 7 Preissner KT, Grulich-Henn J, Ehrlich HJ, Declerck P, Justus C, Collen D, Pannekoek H, Müller-Berghaus G. Structural requirements for the extracellular interaction of plasminogen activator inhibitor 1 with endothelial cell matrix-associated vitronectin. J Biol Chem 1990; 265: 18490-8
    PubMedGoogle Scholar
  • 8 Tschopp J, Masson D, Schafer S, Peitsch M, Preissner KT. The heparin binding domain of S-protein/vitronectin binds to complement components C7, C8, and C9 and perforin from cytolytic T-cells and inhibits their lytic activities. Biochemistry 1988; 27: 4103-9
    CrossrefPubMedGoogle Scholar
  • 9 Suzuki S, Oldberg A, Hayman EG, Pierschbacher MD, Ruoslahti E. Complete amino acid sequence of human vitronectin deduced from cDNA. Similarity of cell attachment sites in vitronectin and fibronectin. EMBO J 1985; 4: 2519-24
    PubMedGoogle Scholar
  • 10 Dahlbôck B, Podack ER. Characterization of human S-protein, an inhibitor of the membrane attack complex of complement. Demonstration of a free reactive thiol group. Biochemistry 1985; 24: 2368-74
    CrossrefPubMedGoogle Scholar
  • 11 Podack ER, Müller-Eberhard HJ. Isolation of human S-protein, an inhibitor of the membrane attack complex of complement. J Biol Chem 1979; 254: 9908-14
    PubMedGoogle Scholar
  • 12 Tollefsen DM, Weigel CJ, Kabeer MH. The presence of methionine of threonine at position 381 in vitronectin is correlated with proteolytic cleavage at arginine 379. J Biol Chem 1990; 265: 9778-81
    PubMedGoogle Scholar
  • 13 Sane DC, Moser TL, Parker CJ, Seiffert D, Loskutoff DJ, Greenberg ÇS. Highly sulfated glycosaminoglycans augment the cross-linking of vitronectin by guinea pig liver transglutaminase. Functional studies of the crosslinked vitronectin multimers: J Biol Chem 1990; 265: 3543-8
    PubMedGoogle Scholar
  • 14 Izumi M, Yamada KM, Hayashi M. Vitronectin exists in two structurally and functionally distinct forms in human plasma. Biochim Biophys Acta 1989; 990: 101-8
    CrossrefPubMedGoogle Scholar
  • 15 Weinstein MJ, Doolittle RF. Differential specificities of thrombin, plasmin and trypsin with regard to synthetic and natural substrates and inhibitors. Biochim Biophys Acta 1972; 258: 577-90
    CrossrefPubMedGoogle Scholar