The Role of Lys-Plasminogen in Cell-Mediated Plasmin Production

  • Lindsey A. Miles
  • Nicholas M. Andronicos
  • Jordi Felez
  • Davida K. Grella
  • Francis J. Castellino
  • Yun Gong

Abstract

A key control point by which the activity of plasmin is positively regulated is by localizing Glu-plasminogen (the native circulating form of the plasminogen molecule) to specific binding sites on cell surfaces. Glu-plasminogen is activated much more efficiently when bound to cells than when in solution. Upon activation, plasmin remains associated with the cell surface where plasmin activity is relatively protected from inhibitors. Furthermore, the enzymatic activity of plasmin is enhanced in the milieu of the cell surface.

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References

  1. Andronicos, N.M. and Ranson, M. (2001). The topology of plasminogen binding and activation on the surface of human breast cancer cells. Br. J. Cancer 85, 909–916.PubMedCrossRefGoogle Scholar
  2. Banyai, L. and Patty, L. (1984). Importance of intramolecular interactions in the control of the fibrin affinity and activation of human plasminogen. J. Biol. Chem. 259, 6466–6471.PubMedGoogle Scholar
  3. Bohmfalk, J.F. and Fuller, G.M. (1980). Plasminogen is synthesized by primary cultures of rat hepatocytes. Science 209, 408–410.PubMedCrossRefGoogle Scholar
  4. Boyle, M.D. and Lottenberg, R. (2000). The interaction of pathogens with humans. Methods 21, 99–102.PubMedCrossRefGoogle Scholar
  5. Christensen, U. and Molgaard, L. (1992). Positive co-operative binding at two weak lysine-binding sites governs the Glu-plasminogen conformational change. Biochem. J. 285, 419–425.PubMedGoogle Scholar
  6. Claeys, H. and Vermylen, J. (1974). Physico-chemical and proenzyme properties of NH2-terminal glutamic acid and NH2-terminal lysine human plasminogen. Influence of 6-aminohexanoic acid. Biochim. Biophys. Acta 342, 351–359.PubMedCrossRefGoogle Scholar
  7. Dudani, A.K. and Ganz, P.R. (1996). Endothelial cell surface actin serves as a binding site for plasminogen, tissue plasminogen activator and lipoprotein(a). Br. J. Haematol. 95, 168–178.PubMedCrossRefGoogle Scholar
  8. Duval-Jobe, C. and Parmely, M.J. (1994). Regulation of plasminogen activation by human U937 promonocytic cells. J. Biol. Chem. 269, 21353–21357.PubMedGoogle Scholar
  9. Ellis, V., Behrendt, N., and Dano, K. (1991). Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor. J. Biol. Chem. 266, 12752–12758.PubMedGoogle Scholar
  10. Ellis, V., Scully, M.F., and Kakkar, V.V. (1989). Plasminogen activation initiated by single-chain urokinase-type plasminogen activator. J. Biol. Chem. 264, 2185–2188.PubMedGoogle Scholar
  11. Félez, J., Miles, L.A., Fábregas, P., Jardi, M., Plow, E.F., and Lijnen, R.H. (1996). Characterization of cellular binding sites and interactive regions within reactants required for enhancement of plasminogen activation by tPA on the surface of leukocytic cells. Thromb. Haemost. 76, 577–584.PubMedGoogle Scholar
  12. Fredenburgh, J.C. and Nesheim, M.E. (1992). Lys-plasminogen is a significant intermediate in the activation of Glu-plasminogen during fibrinolysis in vitro. J. Biol. Chem. 267, 26150–26156.PubMedGoogle Scholar
  13. Gong, Y., Kim, S.-O., Felez, J., Grella, D.K., Castellino, F.J., and Miles, L.A. (2001). Conversion of glu-plasminogen to lys-plasminogen is necessary for optimal stimulation of plasminogen activation on the endothelial cell surface. J. Biol. Chem. 276, 19078–19083.PubMedCrossRefGoogle Scholar
  14. Gonzalez-Gronow, M., Stack, S., and Pizzo, S.V. (1991). Plasmin binding to the plasminogen receptor enhances catalytic efficiency and activates the receptor for subsequent ligand binding. Arch. Biochem. Biophys. 286, 625–628.PubMedCrossRefGoogle Scholar
  15. Grella, D.K. and Castellino, F.J. (1997). Activation of human plasminogen by staphylokinase. Direct evidence that preformed plasmin is necessary for activation to occur. Blood 89, 1585–1589.PubMedGoogle Scholar
  16. Hajjar, K.A., Harpel, P.C., Jaffe, E.A., and Nachman, R.L. (1986). Binding of plasminogen to cultured human endothelial cells. J. Biol. Chem. 261, 11656–11662.PubMedGoogle Scholar
  17. Hajjar, K.A., Jacovina, A.T., and Chacko, J. (1994). An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with annexin II. J. Biol. Chem. 269, 21191–21197.PubMedGoogle Scholar
  18. Hajjar, K.A. and Nachman, R.L. (1988). Endothelial cell-mediated conversion of glu-plasminogen to lys-plasminogen. J. Clin. Invest. 82, 1769–1778.PubMedCrossRefGoogle Scholar
  19. Hawley, S.B., Tamura, T., and Miles, L.A. (2001). Purification, cloning, and characterization of a profibrinolytic plasminogen-binding protein, TIP49a. J. Biol. Chem. 276, 179–186.PubMedCrossRefGoogle Scholar
  20. Hembrough, T.A., Vasudevan, J., Allietta, M.M., Glass, W.F., and Gonias, S.L. (1995). A cytokeratin 8-like protein with plasminogen-binding activity is present on the external surfaces of hepatocytes, HepG2 cells and breast carcinoma cell lines. J. Cell Sci. 108 (Pt. 3), 1071–1082.PubMedGoogle Scholar
  21. Holvoet, P., Lijnen, H.R., and Collen, D. (1985). A monoclonal antibody specific for Lys-plasminogen. Application to the study of the activation pathways of plasminogen in vivo. J. Biol. Chem. 260,12106–12111.PubMedGoogle Scholar
  22. Horrevoets, A.J.G., Smilde, A.E., Fredenburgh, J.C., Pannekoek, H., and Nesheim, M.E. (1995). The activation-resistant conformation of recombinant human plasminogen is stabilized by basic residues in the amino-terminal hinge region. J. Biol. Chem. 270, 15770–15776.PubMedCrossRefGoogle Scholar
  23. Hoylaerts, M., Rijken, D.C., Lijnen, H.R., and Collen, D. (1982). Kinetics of the activation of plasminogen by human tissue plasminogen activator. J. Biol. Chem. 257, 2912–2919.PubMedGoogle Scholar
  24. Jeffery, C.J. (1999). Moonlighting proteins. Trends Biochem. Sci. 24, 8–11.PubMedCrossRefGoogle Scholar
  25. Longstaff, C., Meiton, R.E., Fabregas, P., and Felez, J. (1999). Characterization of cell-associated plasminogen activation catalyzed by urokinase-type plasminogen activator, but independent of urokinase receptor (uPAR, CD87). Blood 93, 3839–3846.PubMedGoogle Scholar
  26. Lopez-Alemany, R., Correc, P., Camoin, L., and Burtin, P. (1994). Purification of the plasmin receptor from human carcinoma cells and comparison to α-enolase. Thromb. Res. 75, 371–381.PubMedCrossRefGoogle Scholar
  27. Loscalzo, J. and Vaughan, D.E. (1987). Tissue plasminogen activator promotes platelet disaggregation in plasma. J. Clin. Invest. 79, 1749–1755.PubMedCrossRefGoogle Scholar
  28. Manchanda, N. and Schwartz, B.S. (1991). Single chain urokinase: Augmentation of enzymatic activity upon binding to monocytes. J. Biol. Chem. 266, 14580–14584.PubMedGoogle Scholar
  29. Mangel, W.F., Lin, B., and Ramakrishnan, V. (1990). Characterization of an extremely large, ligand-induced conformational change in plasminogen. Science 248, 69–73.PubMedCrossRefGoogle Scholar
  30. Markus, G., De Pasquale, J.L., and Wissler, F.C. (1978a). Quantitative determination of the binding of epsilon-aminocaproic acid to native plasminogen. J. Biol. Chem. 253, 727–732.PubMedGoogle Scholar
  31. Markus, G., Evers, J.L., and Hobika, G.H. (1978b). Comparison of some properties of natiave (glu) and modified (lys) human plasminogen. J. Biol. Chem. 253, 733–739.PubMedGoogle Scholar
  32. Markus, G., Priore, R.L., and Wissler, F.C. (1979). The binding of tranexamic acid to native (Glu) and modified (Lys) human plasminogen and its effect on conformation. J. Biol. Chem. 254, 1211–1216.PubMedGoogle Scholar
  33. Miles, L.A., Dahlberg, CM., Levin, E.G., and Plow, E.F. (1989). Gangliosides interact directly with plasminogen and urokinase and may mediate binding of these components to cells. Biochemistry 280, 9337–9343.CrossRefGoogle Scholar
  34. Miles, L.A., Dahlberg, CM., Plescia, J., Felez, J., Kato, K., and Plow, E.F. (1991). Role of cell-surface lysines in plasminogen binding to cells: Identification of alpha-Enolase as a candidate plasminogen receptor. Biochemistry 30, 1682–1691.PubMedCrossRefGoogle Scholar
  35. Miles, L.A., Dahlberg, C.M., and Plow, E.F., (1988). The cell-binding domains of plasminogen and their function in plasma. J. Biol. Chem. 263, 11928–11934.PubMedGoogle Scholar
  36. Miles, L.A., Ginsberg, M.H., White, J.G., and Plow, E.F. (1986). Plasminogen interacts with human platelets through two distinct mechanisms. J. Clin. Invest. 77, 2001–2009.PubMedCrossRefGoogle Scholar
  37. Miles, L.A. and Parmer, R.J. (2001). Neuroendocrine cell plasminogen receptors promote prohormone processing. Thromb. Haemost. 86(Suppl. I).Google Scholar
  38. Miles, L.A. and Plow, E.F. (1985). Binding and activation of plasminogen on the platelet surface. J. Biol. Chem. 260, 4303–4311.PubMedGoogle Scholar
  39. Misselwitz, R., Welfle, K., and Welfle, H. (1994). Conformations and stabilities of human Glul- and Lys78-plasminogen and of the fragments mini- and microplasminogen, analysed by circular dichroism and differential scanning calorimetry. Int. J. Biol. Macromol. 16, 187–194.PubMedCrossRefGoogle Scholar
  40. Muesch, A., Hartmann, E., and Rohde, K. (1990). A novel pathway for secretory proteins? No journal or journal lost.Google Scholar
  41. Nakajima, K., Hamanoue, M., Takemoto, N., Hattori, T., Kato, K., and Kohsaka, S. (1994). Plasminogen binds specifically to alpha-Enolase on rat neuronal plasma membrane. J. Neurochem. 63, 2048–2057.PubMedCrossRefGoogle Scholar
  42. Pancholi, V. and Fischetti, V.A. (1998). α-enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci. J. Biol. Chem. 273, 14503–14515.PubMedCrossRefGoogle Scholar
  43. Parkkinen, J., Raulo, E., Merenmies, J., Nolo, R., Kajander, E.O., Baumann, M., and Rauvala, H. (1993). Amphoterin, the 30-kDa protein in a family of HMGl-type polypeptides. J. Biol. Chem. 268, 19726–19738.PubMedGoogle Scholar
  44. Parmer, R.J., Mahata, M., Gong, Y., Mahata, S.K., Jiang, Q., O’Connor, D.T., Xi, X.-P., and Miles, L.A. (2000). Processing of chromogranin A by plasmin provides a novel mechanism for regulating catecholamine secretion. J. Clin. Invest. 106, 907–915.PubMedCrossRefGoogle Scholar
  45. Ponting, C.P., Holland, S.K., Cederholm-Williams, S.A., Marshall, J.M., Brown, A.J., Spraggon, G., and Blake, C.C. (1992). The compact domain conformation of human Glu-plasminogen in solution. Biochim. Biophys. Acta 1159, 155–161.PubMedCrossRefGoogle Scholar
  46. Ramakrishnan, V., Patthy, L., and Mangel, W.F. (1991). Conformation of Lys-plasminogen and the kringle 1–3 fragment of plasminogen analyzed by small-angle neutron scattering. Biochemistry 30, 3963–3969.PubMedCrossRefGoogle Scholar
  47. Ramakrishnan, V., Sinicropi, D.V., Dere, R., Darbonne, W.C., Bechtol, K.B., and Baker, J.B. (1990). Interaction of wild-type and catalytically inactive mutant forms of tissue-type plasminogen activator with human umbilical vein endothelial cell monolayers. J. Biol. Chem. 265, 2755–2761.PubMedGoogle Scholar
  48. Redlitz, A., Fowler, B.J., Plow, E.F., and Miles, L.A. (1995). The role of an enolase-related molecule in plasminogen binding to cells. Eur. J. Biochem. 227, 407–415.PubMedCrossRefGoogle Scholar
  49. Saito, H., Hamilton, S.M., Tavill, A.S., Louis, L., and Ratnoff, O.D. (1980). Production and release of plasminogen by isolated perfused rat liver. Proc. Natl. Acad. Sci. USA 77, 6837–6840.PubMedCrossRefGoogle Scholar
  50. Sinniger, V., Merton, R.E., Fabregas, P., Felez, J., and Longstaff, C. (1999). Regulation of tissue plasminogen activator activity by cells. J. Biol. Chem. 274, 12414–12422.PubMedCrossRefGoogle Scholar
  51. Sjoholm, I. (1973). Studies on the conformational changes of plasminogen induced during activation to plasmin and by 6-aminohexanoic acid. Eur. J. Biochem. 39, 471–479.PubMedCrossRefGoogle Scholar
  52. Suenson, E. and Thorsen, S. (1998). The course and prerequisites of Lys-plasminogen formation during fibrinolysis, Biochemistry 27, 2435–2443.CrossRefGoogle Scholar
  53. Strieker, R.B., Wong, D., Tak Shiu, D., Reyes, P.T., and Shuman, M.A. (1986). Activation of plasminogen by tissue plasminoagen activator on normal and thrombasthenic platelets: Effects on surface proteins and platelet aggregation. Blood 68, 275–280.Google Scholar
  54. Thorsen, S. and Astrup, T. (1974). Substrate composition and the effect of epsilon-aminocaproic acid on tissue plasminogen activator and urokinase-induced fibrinolysis. Thromb. Diath. Haemorrh. 32, 306–324.PubMedGoogle Scholar
  55. Thorsen, S., Kok, P., and Astrup, T. (1974). Reversible and irreversible alterations of human plasminogen indicated by changes in susceptibility to plasminogen activators and in response to epsilon-aminocaproic acid. Thromb. Diath. Haemorrh. 32, 325–340.PubMedGoogle Scholar
  56. Thorsen, S. and Mullertz, S. (1974). Rate of activation and electrophoretic mobility of unmodified and partially degraded plasminogen. Effects of 6-aminohexanoic acid and related compounds. Scand. J. Clin. Lab. Invest. 34, 167–176.PubMedCrossRefGoogle Scholar
  57. Violand, B.N. and Castellino, F.J. (1976). Mechanism of the urokinase-catalyzed activation of human plasminogen. J. Biol. Chem. 251, 3906–3912.PubMedGoogle Scholar
  58. Violand, B.N., Sodetz, J.M., and Castellino, F.J. (1975). The effect of epsilon-amino caproic acid on the gross conformation of plasminogen and plasmin. Arch. Biochom. Biophys. 170, 300–305.CrossRefGoogle Scholar
  59. Weisel, J.W., Nagaswami, C., Korsholm, B., Petersen, L.C., and Suenson, E. (1994). Interactions of plasminogen with polymerizing fibrin and its derivatives, monitored with a photoaffinity cross-linker and electron microscopy. J. Mol. Biol. 235, 1117–1135.PubMedCrossRefGoogle Scholar
  60. Wiman, B. (1973). Primary structure of peptides released during activation of human plasminogen by urokinase.Eur. J. Biochem. 39, 1–9.PubMedCrossRefGoogle Scholar
  61. Wiman, B. and Wallen, P. (1975). Structural relationship between “glutamic acid” and “lysine” forms of human plasminogen and their interaction with the NH2-terminal activation peptide as studied by affinity chromatography.Eur. J. Biochem. 50, 489–494.PubMedCrossRefGoogle Scholar
  62. Winram, S.B. and Lottenberg, R. (1996). The plasmin-binding protein Plr of group A streptococci is identified as glyceraldehyde-3-phosphate dehydrogenase. Microbiology 142, 2311–2320.PubMedCrossRefGoogle Scholar
  63. Wistow, G. and Piatigorsky, J. (1987). Recruitment of enzymes as lens structural proteins. Science 236,1554–1556.PubMedCrossRefGoogle Scholar
  64. Zhang, L., Seiffert, D., Fowler, B., Jenkins, G.R., Thinnes, T., Loskutoff, D.J., Parmer, R.J., and Miles, L.A.(2002). Plasminogen has a broad extrahepatic distribution. Thromb. Haemost. 87, 493–501.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Lindsey A. Miles
    • 1
  • Nicholas M. Andronicos
    • 1
  • Jordi Felez
    • 2
  • Davida K. Grella
    • 3
  • Francis J. Castellino
    • 3
  • Yun Gong
    • 1
  1. 1.Department of Cell Biology, Division of Vascular BiologyThe Scripps Research InstituteLa JollaUSA
  2. 2.Institut de Recerca OncologicaBarcelonaSpain
  3. 3.The University of Notre DameNotre DameUSA

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