Download PDF
Thromb Haemost 1991; 66(01): 088-110
DOI: 10.1055/s-0038-1646377
Review Article
Schattauer GmbH Stuttgart

Strategies for the Improvement of Thrombolytic Agents

H R Lijnen
,
D Collen
Further Information

Publication History

Publication Date:
25 July 2018 (online)

  PDF Download  Permissions and Reprints
 

  • References

  • 1 Collen D, Lijnen HR. Molecular mechanisms of thrombolysis: implications for therapy. Biochemical Pharmacology 1990; 40: 177-86
    CrossrefPubMedGoogle Scholar
  • 2 Wiman B, Collen D. Molecular mechanism of physiological fibrinolysis. Nature 1978; 272: 549-50
    CrossrefPubMedGoogle Scholar
  • 3 Pennica D, Holmes WE, Kohr WJ, Harkins RN, Vehar GA, Ward CA, Bennett WF, Yelverton E, Seeburg PH, Heyneker HL, Goeddel DV, Collen D. Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature 1983; 301: 214-21
    PubMedGoogle Scholar
  • 4 Vehar GA, Spellman MW, Keyt BA, Ferguson CK, Keck RG, Chloupek RC, Harris R, Bennett WF, Builder SE, Hancock WS. Characterization studies of human tissue-type plasminogen activator produced by recombinant DNA technology. Cold Spring Harbor Symposia on Quantitative Biology 1986; LI: 551-62
    PubMedGoogle Scholar
  • 5 Holmes WE, Pennica D, Blaber M, Rey MW, Guenzler WA, Steffens GJ, Heyneker HL. Cloning and expression of the gene for pro-urokinase in Escherichia coli. Biotechnology 1985; 3: 923-9
    CrossrefPubMedGoogle Scholar
  • 6 Winkler ME, Blaber M, Bennett WF, Holmes W, Vehar GA. Purification and characterization of recombinant urokinase from Escherichia coli. Biotechnology 1985; 3: 990-1000
    CrossrefPubMedGoogle Scholar
  • 7 Collen D. Coronary thrombolysis: streptokinase or recombinant tissue-type plasminogen activator?. Ann Intern Med 1990; 112: 529-38
    CrossrefPubMedGoogle Scholar
  • 8 Topol EJ, Califf RM, George BS, Kereiakes DJ, Rothbaum D, Candela RJ, Abbotsmith CW, Pinkerton CA, Stump DC, Collen D, Lee KL, Pitt B, Kline EM, Boswick JM, O'Neill WW, Stack RS. Coronary arterial thrombolysis with combined infusion of recombinant tissue-type plasminogen activator and urokinase in acute myocardial infarction. Circulation 1988; 77: 1100-7
    CrossrefPubMedGoogle Scholar
  • 9 Rentrop KP. Thrombolytic therapy in patients with acute myocardial infarction. Circulation 1985; 71: 627-31
    CrossrefPubMedGoogle Scholar
  • 10 Chesebro JH, Knatterud G, Braunwald E. Thrombolytic therapy. N Engl J Med 1988; 319: 1544-5
    PubMedGoogle Scholar
  • 11 Gold HK, Leinbach RC, Palacios IF, Yasuda T, Block PC, Buckley MJ, Akins CW, Daggett WM, Austen WG. Coronary reocclusion after selective administration of streptokinase. Circulation 1983; 68: 150-4
    PubMedGoogle Scholar
  • 12 Raynaud P, Desveaux B. Réocclusion après traitement par l'Actilyse. Arch Mai Coeur 1988; 81 (Suppl 1) 25-32
    PubMedGoogle Scholar
  • 13 The International Study Group. In-hospital mortality and clinical course of 20,891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. Lancet 1990; 336: 71-5
    CrossrefPubMedGoogle Scholar
  • 14 Collen D, Gold HK. Fibrin-specific thrombolytic agents and new approaches to coronary arterial thrombolysis. in Julian D, Kübler W, Norris RM, Swan HJC, Collen D, Verstraete M. (eds) Thrombolysis in Cardiovascular Disease. New York, Marcel Dekker Inc: 1990. p 45-67
    Google Scholar
  • 15 Pannekoek H, Lijnen HR, Loskutoff DJ. Recommendations for the nomenclature of mutant fibrinolytic genes and their proteins. Thromb Haemost 1990; 64: 600-3
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Rijken DC, Wijngaards G, Zaal-De Jong M, Welbergen J. Purification and partial characterization of plasminogen activator from human uterine tissue. Biochim Biophys Acta 1979; 580: 140-53
    CrossrefPubMedGoogle Scholar
  • 17 Rijken DC, Wijngaards G, Welbergen J. Relationship between tissue plasminogen activator and the activators in blood and vascular wall. Thromb Res 1980; 18: 815-30
    CrossrefPubMedGoogle Scholar
  • 18 Levine EG, Loskutoff DJ. Cultured bovine endothelial cells produce both urokinase and tissue-type plasminogen activators. J Cell Biol 1982; 94: 631-6
    CrossrefPubMedGoogle Scholar
  • 19 Rijken DC, Collen D. Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. J Biol Chem 1981; 256: 7035-41
    PubMedGoogle Scholar
  • 20 Collen D, Rijken DC, Van Damme J, Billiau A. Purification of human tissue-type plasminogen activator in centigram quantities from human melanoma cell culture fluid and its conditioning for use in vivo. . Thromb Haemost 1982; 48: 294-6
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Kruithof EKO, Schleuning WD, Bachmann F. Human tissue-type plasminogen activator. Production in continuous serum-free cell culture and rapid purification. Biochem J 1985; 226: 631-6
    PubMedGoogle Scholar
  • 22 Edlund T, Ny T, Rånby M, Heden LO, Palm G. Holmgren E, Josephson S. Isolation of cDNA sequences coding for a part of human tissue plasminogen activator. Proc Natl Acad Sci USA 1983; 80: 349-52
    CrossrefPubMedGoogle Scholar
  • 23 Fisher R, Waller EK, Grossi G, Thompson D, Tizard R, Schleuning WD. Isolation and characterization of the human tissue-type plasminogen activator structural gene including its 5'-flanking region. J Biol Chem 1985; 260: 11223-30
    PubMedGoogle Scholar
  • 24 Kaufman R, Wasley LC, Spiliotes AJ, Gossels SD, Latt SA, Larson GR, Kay RM. Coamplification and coexpression of human tissue-type plasminogen activator and murine dihydrofolate reductase sequences in Chinese hamster ovary cells. Mol Cell Biol 1985; 5: 1750-9
    CrossrefPubMedGoogle Scholar
  • 25 Harris TJR, Patel T, Marston FAO, Little S, Emtage JS, Opdenakker G, Volckaert G, Rombauts W, Billiau A, De Somer P. Cloning of cDNA coding for human tissue-type plasminogen activator and its expression in Escherichia coli. Mol Biol Med 1986; 3: 279-92
    PubMedGoogle Scholar
  • 26 Sambrook J, Hanahan D, Rodgers L, Gething MJ. Expression of human tissue-type plasminogen activator from lytic viral vectors and in established cell lines. Mol Biol Med 1986; 3: 459-81
    PubMedGoogle Scholar
  • 27 Sarmientos P, Duchesne M, Denefle P, Boiziau J, Fromage N, Delporte N, Parker F, Lelievre Y, Mayaux JF, Cartwrigth T. Synthesis and purification of active human tissue plasminogen activator from Escherichia coli. Biotechnology 1989; 7: 495-501
    CrossrefPubMedGoogle Scholar
  • 28 Builder SE, Grossbard E. Laboratory and clinical experience with recombinant plasminogen activator. in Murawski Peetoom. (eds) Transfusion Medicine: Recent technological advances. New York, A.R. Liss: 1986. p 303-313
    Google Scholar
  • 29 Jörnvall H, Pohl G, Bergsdorf N, Wallen P. Differential proteolysis and evidence for a residue exchange in tissue plasminogen activator suggest possible association between two types of protein microheterogeneity. FEBS Lett 1983; 156: 47-50
    CrossrefPubMedGoogle Scholar
  • 30 Banyai L, Varadi A, Patthy L. Common evolutionary origin of the fibrin-binding structures of fibronectin and tissue-type plasminogen activator. FEBS Lett 1983; 163: 37-41
    CrossrefPubMedGoogle Scholar
  • 31 Spellman MW, Basa LJ, Leonard CK, Chakel JA, O'Connor JV, Wilson S, van Halbeek H. Carbohydrate structures of human tissue plasminogen activator expressed in Chinese hamster ovary cells. J Biol Chem 1989; 264: 14100-11
    PubMedGoogle Scholar
  • 32 Parekh RB, Dwek RA, Rudd PM, Thomas JR, Rademacher TW, Warren T, Wun TC, Hebert B, Reitz B, Palmier M, Ramabhadran T, Tiemeier DC. N-glycosylation and in vitro enzymatic activity of human recombinant tissue plasminogen activator expressed in Chinese hamster ovary cells and a murine cell line. Biochemistry 1989; 28: 7670-9
    CrossrefPubMedGoogle Scholar
  • 33 Parekh RB, Dwek RA, Thomas JR, Opdenakker G, Rademacher TW, Wittwer AJ, Howard SC, Nelson R, Siegel NR, Jennings MG, Harakas NK, Feder J. Cell-type-specific and site-specific N-glycosylation of type I and type II human tissue plasminogen activator. Biochemistry 1989; 28: 7644-62
    CrossrefPubMedGoogle Scholar
  • 34 Bennett WF, Paoni NF, Sethy I, Kerr E, Pena L, Keyt B, Nguyen H, Baldini L, Jones A, Meunier A, Wurm F, Johnson A, Zoller MJ, Higgins JD, Botstein D. Mapping the functional determinants of tissue-plasminogen activator.. Fibrinolysis 1990; 4 (Suppl 3) 14 (Abstract 37)
    PubMedGoogle Scholar
  • 35 Bennett WF, Paoni NF, Keyt BA, Botstein D, Jones AJS, Presta L, Wurm FM, Zoller MJ. High resolution analysis of functional determinants on human tissue-type plasminogen activator. J Biol Chem (in press)
    PubMedGoogle Scholar
  • 36 Rajput B, Degen SF, Reich E, Waller EK, Axelrod J, Eddy RL, Shows TB. Chromosomal locations of human tissue plasminogen activator and urokinase genes. Science 1985; 230: 672-4
    CrossrefPubMedGoogle Scholar
  • 37 Verheijen JH, Visse R, Wijnen JT, Chang GTG, Kluft C, Meera Khan P. Assignment of the human tissue-type plasminogen activator gene (PLAT) to chromosome 8. Hum Genet 1986; 72: 153-6
    PubMedGoogle Scholar
  • 38 Yang-Feng TL, Opdenakker G, Volckaert G, Francke U. Human tissue-type plasminogen activator gene located near chromosomal breakpoint in myeloproliferative disorder. Am J Hum Genet 1986; 39: 79-87
    PubMedGoogle Scholar
  • 39 Ny T, Elgh F, Lund B. The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains. Proc Natl Acad Sci USA 1984; 81: 5355-9
    CrossrefPubMedGoogle Scholar
  • 40 Browne MJ, Tyrrell AWR, Chapman CG, Carrey JE, Glover DM, Grosveld FG, Dodd I, Robinson JH. Isolation of a human tissue-type plasminogen activator genomic DNA clone and its expression in mouse L cells. Gene 1985; 33: 279-84
    CrossrefPubMedGoogle Scholar
  • 41 Degen SJF, Rajput B, Reich E. The human tissue plasminogen activator gene. J Biol Chem 1986; 261: 6972-85
    PubMedGoogle Scholar
  • 42 Patthy L. Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules. Cell 1985; 41: 657-63
    CrossrefPubMedGoogle Scholar
  • 43 Pannekoek H, de Vries C, van Zonneveld AJ. Mutants of human tissue-type plasminogen activator (t-PA): structural aspects and functional properties. Fibrinolysis 1988; 2: 123-32
    PubMedGoogle Scholar
  • 44 Rijken DC, Groeneveld E. Isolation and functional characterization of the heavy and light chains of human tissue-type plasminogen activator. J Biol Chem 1986; 261: 3098-102
    PubMedGoogle Scholar
  • 45 Holvoet P, Lijnen HR, Collen D. Characterization of functional domains in human tissue-type plasminogen activator with the use of monoclonal antibodies. Eur J Biochem 1986; 158: 173-7
    CrossrefPubMedGoogle Scholar
  • 46 van Zonneveld AJ, Veerman H, Pannekoek H. On the interaction of the finger and kringle-2 domain of tissue-type plasminogen activator with fibrin. J Biol Chem 1986; 261: 14214-8
    PubMedGoogle Scholar
  • 47 Kagitani H, Tagawa M, Hatanaka K, Ikari T, Saito A, Bando H, Okada K, Matsuo O. Expression in E. coli of finger-domain lacking tissue-type plasminogen activator with high fibrin affinity. FEBS Lett 1985; 189: 145-9
    PubMedGoogle Scholar
  • 48 Larsen GR, Henson K, Blue Y. Variants of human tissue-type plasminogen activator. Fibrin binding, fibrinolytic, and fibrinogenolytic characterization of genetic variants lacking the fibronectin finger-like and/or the epidermal growth factor domains. J Biol Chem 1988; 263: 1023-9
    PubMedGoogle Scholar
  • 49 van Zonneveld AJ, Veerman H, Pannekoek H. Autonomous functions of structural domains on human tissue-type plasminogen activator. Proc Natl Acad Sci USA 1986; 83: 4670-4
    CrossrefPubMedGoogle Scholar
  • 50 Kalyan NK, Lee SG, Wilhelm J, Fu KP, Hum WT, Rappaport R, Hartzell RW, Urbano C, Hung PP. Structure-function analysis with tissue-type plasminogen activator. Effect of deletion of NH2-terminal domains on its biochemical and biological properties. J Biol Chem 1988; 263: 3971-8
    PubMedGoogle Scholar
  • 51 Verheijen JH, Caspers MPM, Chang GTG, De Munck GAW, Pouwels PH, Enger-Valk BE. Involvement of finger domain and kringle 2 domain of tissue-type plasminogen activator in fibrin binding and stimulation of activity by fibrin. EMBO J 1986; 5: 3525-30
    PubMedGoogle Scholar
  • 52 Ichinose A, Takio K, Fujikawa K. Localization of the binding site of tissue-type plasminogen activator to fibrin. J Clin Invest 1986; 78: 163-9
    CrossrefPubMedGoogle Scholar
  • 53 de Munk GAW, Caspers MPM, Chang GTG, Pouwels PH, Enger-Valk BE, Verheijen JH. Binding of tissue-type plasminogen activator to lysine, lysine analogues, and fibrin fragments. Biochemistry 1989; 28: 7318-7325
    CrossrefPubMedGoogle Scholar
  • 54 Weening-Verhoeff EJD, Quax PHA, Van Leeuwen RTJ, Rehberg EF, Marotti KR, Verheijen JH. Involvement of aspartic and glutamic residues in kringle-2 of tissue-type plasminogen activator in lysine binding, fibrin binding and stimulation of activity as revealed by chemical modification and oligonucleotide-directed mutagenesis. Protein Eng 1990; 4: 191-8
    CrossrefPubMedGoogle Scholar
  • 55 Verheijen JH, Bakker AJ, Weening-Verhoeff EJD, Marotti KR, Rehberg E. Creation of a binding site for lysine and fibrin in kringle-1 of tissue-type plasminogen activator by substitution of six consecutive amino acid residues by the residues from the homologous kringle-2.. Fibrinolysis 1990; 4 (Suppl 3) 165 (Abstract 428)
    PubMedGoogle Scholar
  • 56 Verheijen JH, Caspers MPM, de Munk GAW, Enger-Valk BE, Chang GTG, Verwels PH. Sites in tissue-type plasminogen activator involved in the interaction with fibrin, plasminogen and low molecular weight ligands.. Thromb Haemost 1987; 58: 491 (Abstract 1814)
    Article in Thieme ConnectPubMedGoogle Scholar
  • 57 Christensen U. The AH-site of plasminogen and two C-terminal fragments; A weak lysine-binding site preferring ligands not carrying a free carboxylate function. Biochem J 1984; 223: 413-21
    CrossrefPubMedGoogle Scholar
  • 58 Cleary S, Mulkerrin MG, Kelley RF. Purification and characterization of tissue plasminogen activator kringle-2 domain expressed in Escherichia coli. Biochemistry 1989; 28: 1884-91
    CrossrefPubMedGoogle Scholar
  • 59 de Vries C, Veerman H, Pannekoek H. Identification of the domains of tissue-type plasminogen activator involved in the augmented binding to fibrin after limited digestion with plasmin. J Biol Chem 1989; 264: 12604-10
    PubMedGoogle Scholar
  • 60 de Vries C, Veerman H, Koornneef E, Pannekoek H. Tissue-type plasminogen activator and its substrate Glu-plasminogen share common binding sites in limited plasmin-digested fibrin. J Biol Chem 1990; 265: 13547-52
    PubMedGoogle Scholar
  • 61 Hoylaerts M, Rijken DC, Lijnen HR, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem 1982; 257: 2912-9
    PubMedGoogle Scholar
  • 62 Nieuwenhuizen W, Voskuilen M, Vermond A, Hoegee-De Nobel B, Traas DW. The influence of fibrin(ogen) fragments on the kinetic parameters of the tissue-type plasminogen-activator-mediated activation of different forms of plasminogen. Eur J Biochem 1988; 174: 163-9
    CrossrefPubMedGoogle Scholar
  • 63 Rijken DC, Hoylaerts M, Collen D. Fibrinolytic properties of one-chain and two-chain human extrinsic (tissue-type) plasminogen activator. J Biol Chem 1982; 257: 2920-5
    PubMedGoogle Scholar
  • 64 Rånby M, Bergsdorf N, Norrman B, Suenson E, Wallen P. Tissue plasminogen activator kinetics,. in. Davidson JF, Bachmann F, Bouvier CA, Kruithof EKO. (eds) Progress in Fibrinolysis, vol 6.. Edinburgh, Churchill Livingstone: 1983. p 182-4
    Google Scholar
  • 65 Suenson E, Lützen O, Thorsen S. Initial plasmin-degradation of fibrin as the basis of a positive feed-back mechanism in fibrinolysis. Eur J Biochem 1984; 140: 513-22
    CrossrefPubMedGoogle Scholar
  • 66 Wallen P, Bergsdorf N, Rånby M. Purification and identification of two structural variants of porcine tissue plasminogen activator by affinity adsorption on fibrin. Biochim Biophys Acta 1982; 719: 318-28
    CrossrefPubMedGoogle Scholar
  • 67 Lijnen HR, Van Hoef B, De Cock F, Collen D. Effect of fibrin-like stimulators on the activation of plasminogen by tissue-type plasminogen activator (t-PA). Studies with active site mutagenized plasminogen and plasmin resistant t-PA. Thromb Haemost 1990; 64: 61-8
    PubMedGoogle Scholar
  • 68 Einarsson M, Brandt J, Kaplan L. Large-scale purification of human tissue-type plasminogen activator using monoclonal antibodies. Biochim Biophys Acta 1985; 830: 1-10
    CrossrefPubMedGoogle Scholar
  • 69 Wittwer AJ, Howard SC, Carr LS, Harakas NK, Feder J, Parekh RB, Rudd PM, Dwek RA, Rademacher TW. Effects of N-glycosylation on in vitro activity of Bowes melanoma and human colon fibroblast derived tissue plasminogen activator. Biochemistry 1989; 28: 7662-9
    CrossrefPubMedGoogle Scholar
  • 70 Miles LA, Plow EF. Binding and activation of plasminogen on the platelet surface. J Biol Chem 1985; 260: 4303-11
    PubMedGoogle Scholar
  • 71 Vaughan DE, Mendelsohn ME, Declerck PJ, Van Houtte E, Collen D, Loscalzo J. Characterization of the binding of human tissue-type plasminogen activator to platelets. J Biol Chem 1989; 264: 15869-74
    PubMedGoogle Scholar
  • 72 Silverstein RL, Nachman RL, Leung LL, Harpel PC. Activation of immobilized plasminogen by tissue activator. Multimolecular complex formation. J Biol Chem 1985; 260: 10346-52
    PubMedGoogle Scholar
  • 73 Hajjar KA, Harpel PC, Jaffe EA, Nachman RL. Binding of plasminogen to cultured human endothelial cells. J Biol Chem 1986; 261: 11656-62
    PubMedGoogle Scholar
  • 74 Hajjar KA, Hamel NM, Harpel PC, Nachman RL. Binding of tissue plasminogen activator to cultured human endothelial cells. J Clin Invest 1987; 80: 1712-9
    CrossrefPubMedGoogle Scholar
  • 75 Hajjar KA, Hamel NM. Identification and characterization of human endothelial cell membrane binding sites for tissue plasminogen activator and urokinase. J Biol Chem 1990; 265: 2908-16
    PubMedGoogle Scholar
  • 76 Barnathan ES, Kuo A, Van der Keyl H, McCrae KR, Larsen GR, Cines DB. Tissue-type plasminogen activator binding to human endothelial cells. Evidence for two distinct binding sites. J Biol Chem 1988; 263: 7792-9
    PubMedGoogle Scholar
  • 77 Stack S, Gonzales-Gronow M, Pizzo SV. Regulation of plasminogen activation by components of the extracellular matrix. Biochemistry 1990; 29: 4966-70
    CrossrefPubMedGoogle Scholar
  • 78 Camiolo SM, Thorsen S, Astrup T. Fibrinogenolysis and fibrinolysis with tissue plasminogen activator, urokinase, streptokinase-activated human globulin, and plasmin. Proc Soc Exper Biol Med 1971; 138: 277-80
    CrossrefPubMedGoogle Scholar
  • 79 Wiman B, Collen D. On the kinetics of the reaction between human antiplasmin and plasmin. Eur J Biochem 1978; 84: 573-8
    CrossrefPubMedGoogle Scholar
  • 80 Higgins DL, Vehar GA. Interaction of one-chain and two-chain tissue plasminogen activator with intact and plasmin-degraded fibrin. Biochemistry 1987; 26: 7786-91
    CrossrefPubMedGoogle Scholar
  • 81 Suenson E, Petersen LC. Fibrin and plasminogen structures essential to stimulation of plasmin formation by tissue-type plasminogen activator. Biochim Biophys Acta 1986; 870: 510-9
    CrossrefPubMedGoogle Scholar
  • 82 Suenson E, Bjerrum P, Holm A, Lind B, Meldal M, Selmer J, Petersen LC. The role of fragment X polymers in the fibrin enhancement of tissue plasminogen activator-catalyzed plasmin formation. J Biol Chem 1990; 265: 2228-37
    PubMedGoogle Scholar
  • 83 Johannessen M, Diness V, Pingel K, Petersen LK, Rao D, Lioubin P, O'Hara P, Mulvihill E. Fibrin affinity and clearance of t-PA deletion and substitution analogues. Thromb Haemostas 1990; 63: 54-9
    PubMedGoogle Scholar
  • 84 Lijnen HR, Nelles L, Van Hoef B, De Cock F, Collen D. Biochemical and functional characterization of human tissue-type plasminogen activator variants obtained by deletion and/or duplication of structural/functional domains. J Biol Chem 1990; 265: 5677-83
    PubMedGoogle Scholar
  • 85 Collen D, Lijnen HR, Vanlinthout I, Kieckens L, Nelles L, Stassen JM. Thrombolytic and pharmacokinetic properties of human tissue-type plasminogen activator variants, obtained by deletion and/or duplication of structural/functional domains, in a hamster pulmonary embolism model. Thromb Haemost 1991; 65: 174-80
    Article in Thieme ConnectPubMedGoogle Scholar
  • 86 Wilhelm J, Kalyan NK, Lee SG, Hum WT, Rappaport R, Hung PP. Deglycosylation increases the fibrinolytic activity of a deletion mutant of tissue-type plasminogen activator. Thromb Haemost 1990; 63: 464-71
    Article in Thieme ConnectPubMedGoogle Scholar
  • 87 Stern A, Mattes R, Buckel P, Weidle UH. Functional topology of human tissue-type plasminogen activator: characterization of two deletion derivatives and of a duplication derivative. Gene 1989; 79: 333-44
    CrossrefPubMedGoogle Scholar
  • 88 Kalyan NK, Wilhelm J, Lee SG, Dheer SK, Cheng S, Hjorth R, Pierzchala WA, Wiener F, Hung PP. Construction, expression and biochemical characterisation of a novel triskringle plasminogen activator gene. Fibrinolysis 1990; 4: 79-86
    PubMedGoogle Scholar
  • 89 Markland W, Pollock D, Livingston DJ. Tissue-type plasminogen activator variants with domain duplications and rearrangements. Prot Engineer 1989; 3: 111-6
    CrossrefPubMedGoogle Scholar
  • 90 Markland W, Pollock D, Livingston DJ. Structure-function analysis of tissue-type plasminogen activator by linker-insertion, point and deletion mutagenesis. Prot Engineer 1989; 3: 117-25
    CrossrefPubMedGoogle Scholar
  • 91 Collen D, Lijnen HR, Bulens F, Vandamme AM, Tulinsky A, Nelles L. Biochemical and functional characterization of human tissue-type plasminogen activator variants with mutagenized kringle domains. J Biol Chem 1990; 265: 12184-91
    PubMedGoogle Scholar
  • 92 Tate KM, Higgins DL, Holmes WE, Winkler ME, Heyneker HL, Vehar GA. Functional role of proteolytic cleavage at Arginine-275 of human tissue plasminogen activator as assessed by site-directed mutagenesis. Biochemistry 1987; 26: 338-43
    CrossrefPubMedGoogle Scholar
  • 93 Urano S, Metzger AR, Castellino FJ. Plasmin-mediated fibrinolysis by variant recombinant tissue plasminogen activators. Proc Natl Acad Sci USA 1989; 86: 2568-71
    CrossrefPubMedGoogle Scholar
  • 94 Petersen LC, Johannessen M, Foster D, Kumar A, Mulvihill E. The effect of polymerized fibrin on the catalytic activities of one-chain tissue-type plasminogen activator as revealed by an analogue resistant to plasmin cleavage. Biochim Biophys Acta 1988; 952: 245-54
    CrossrefPubMedGoogle Scholar
  • 95 Higgins DL, Young SL, Wong A. One chain variants of tissue plasminogen activator have increased susceptibility to inactivation by plasmin. Fibrinolysis 1991; 5: 43-9
    PubMedGoogle Scholar
  • 96 Haigwood NL, Mullenbach GT, Moore GK, DesJardin LE, Tabrizi A, Brown-Shimer SL, Stauss H, Stoehr HA, Paques EP. Variants of human tissue-type plasminogen activator substituted at the protease cleavage site and glycosylation sites, and truncated at the N- and C-termini. Prot Engineer 1989; 2: 611-20
    CrossrefPubMedGoogle Scholar
  • 97 Higgins DL, Lamb MC, Young SL, Powers D, Anderson S. Characterization of tissue plasminogen activator variants with all amino acid possibilities at position 275.. Fibrinolysis 1988; 2 (Suppl 1) 123 (Abstract 279)
    PubMedGoogle Scholar
  • 98 Boose JA, Kuismanen E, Gerard R, Sambrook J, Gething MJ. The single-chain form of tissue-type plasminogen activator has catalytic activity: studies with a mutant enzyme that lacks the cleavage site. Biochemistry 1989; 28: 635-43
    CrossrefPubMedGoogle Scholar
  • 99 Eisert WG, Müller TH. In vitro and in vivo activity of single chain rt-PA-mutant.. Fibrinolysis 1988; 2 (Suppl 1) 52 (Abstract 118)
    PubMedGoogle Scholar
  • 100 Freer ST, Kraut J, Robertus JD, Wright HT, Xuong NH. Chymotrypsinogen: 2.5-angström crystal structure, comparison with alpha-chymotrypsin, and implications for zymogen activation. Biochemistry 1970; 9: 1997-2009
    CrossrefPubMedGoogle Scholar
  • 101 Wallen P, Pohl G, Bergsdorf N, Rånby M, Ny T, Jörnvall H. Purification and characterization of a melanoma cell plasminogen activator. Eur J Biochem 1983; 132: 681-6
    CrossrefPubMedGoogle Scholar
  • 102 Petersen LC, Boel E, Johannessen M, Foster D. Quenching of the amidolytic activity of one-chain tissue-type plasminogen activator by mutation of lysine-416. Biochemistry 1990; 29: 3451-7
    CrossrefPubMedGoogle Scholar
  • 103 Gething MJ, Adler B, Boose JA, Gerard RD, Madison EL, McGookey D, Meidell RS, Roman LM, Sambrook J. Variants of human tissue-type plasminogen activator that lack specific structural domains of the heavy chain. EMBO J 1988; 7: 2731-40
    PubMedGoogle Scholar
  • 104 Ehrlich HJ, Bang NU, Little SP, Jaskunas SR, Weigel BJ, Mattler LE, Harms CS. Biological properties of a kringleless tissue plasminogen activator (t-PA) mutant. Fibrinolysis 1987; 1: 75-81
    PubMedGoogle Scholar
  • 105 Burck PJ, Berg DH, Warrick MW, Berg DT, Walls JD, Jaskunas SR, Crisel RM, Weigel B, Vlahos CJ, McClure DB, Grinnell BW. Characterization of a modified human tissue plasminogen activator comprising a kringle-2 and a protease domain. J Biol Chem 1990; 265: 5170-7
    PubMedGoogle Scholar
  • 106 Jackson CV, Crowe VG, Craft TJ, Sundboom JL, Grinnell BW, Bobbitt JL, Burck PJ, Quay JF, Smith GF. Thrombolytic activity of a novel plasminogen activator, LY210825, compared with recombinant tissue-type plasminogen activator in a canine model of coronary artery thrombosis. Circulation 1990; 82: 930-40
    CrossrefPubMedGoogle Scholar
  • 107 Pohl G, Sterky C, Attersand A, Nyberg E, Loewenadler B, Hansson L. Tissue plasminogen activator mutants lacking the growth factor domain and the first kringle domain: I. DNA constructions, expression in mammalian cells, protein structure, fibrin affinity and enzymatic properties. Fibrinolysis 1991; 5: 17-29
    PubMedGoogle Scholar
  • 108 Wikström K, Mattsson C, Sterky C, Pohl G. Tissue plasminogen activator mutants lacking the growth factor domain and the first kringle domain: II. Enzymatic properties in plasma and in vivo thrombolytic activity and clearance rates in rabbits. Fibrinolysis 1991; 5: 31-41
    PubMedGoogle Scholar
  • 109 Wu Z, Van de Werf F, Stassen T, Matsson C, Pohl G, Collen D. Pharmacokinetics and coronary thrombolytic properties of two human tissue-type plasminogen activator variants lacking the finger-like, growth factor-like, and first kringle domains (amino acids 6-173) in a canine model. J Cardiovasc Pharmacol 1990; 16: 197-203
    CrossrefPubMedGoogle Scholar
  • 110 Gardell SJ, Duong LT, Diehl RE, York JD, Hare TR, Register RB, Jacobs JW, Dixon RAF, Friedman PA. Isolation, characterization, and cDNA cloning of a vampire bat salivary plasminogen activator. J Biol Chem 1989; 264: 17947-52
    PubMedGoogle Scholar
  • 111 Shebuski RJ, Fujita T, Ramjit DR, Stabilito IJ, Cuca GC, Gould SL, Wang S, Tung J-S, Mark GE, Ellis RW, Silberklang M, Gardell SJ. Thrombolytic efficacy of i.v. bolus vampire bat salivary plasminogen activator (bPA) in a rabbit model of femoral arterial thrombosis: comparison to tissue-type plasminogen activator (t-PA).. Fibrinolysis 1990; 4 (Suppl 3) 97 (Abstract 248)
    PubMedGoogle Scholar
  • 112 Kruithof EKO. Plasminogen activator inhibitors - A review. Enzyme 1988; 40: 113-21
    CrossrefPubMedGoogle Scholar
  • 113 Monge JC, Lucore CL, Fry ETA, Sobel BE, Billadello JJ. Characterization of interaction of active-site serine mutants of tissue-type plasminogen activator with plasminogen activator inhibitor-1. J Biol Chem 1989; 264: 10922-5
    PubMedGoogle Scholar
  • 114 Lijnen HR, Van Hoef B, Collen D. On the reversible interaction of plasminogen activator inhibitor-1 with tissue-type plasminogen activator and with urokinase-type plasminogen activator. J Biol Chem (in press)
    PubMedGoogle Scholar
  • 115 de Serrano VS, Castellino FJ. Structural determinants of the noncatalytic chain of tissue-type plasminogen activator that modulate its association rate with plasminogen activator inhibitor-1. J Biol Chem 1990; 265: 10473-8
    PubMedGoogle Scholar
  • 116 Madison EL, Goldsmith EJ, Gerard RD, Gething MJH, Sambrook JF. Serpinresistant mutants of human tissue-type plasminogen activator. Nature 1989; 339: 721-4
    CrossrefPubMedGoogle Scholar
  • 117 Madison EL, Goldsmith EJ, Gerard RD, Gething MJH, Sambrook JF, Bassel-Duby RS. Amino acid residues that affect interaction of tissue-type plasminogen activator with plasminogen activator inhibitor 1. Proc Natl Acad Sci USA 1990; 87: 3530-3
    CrossrefPubMedGoogle Scholar
  • 118 Sambrook JF, Bassel-Duby R, Gerard R, Gething MJ, Goldsmith B, Madison E. Interactions between tissue-type plasminogen activator and its serpin PAI-1.. Fibrinolysis 1990; 4 (Suppl 3) 92 (Abstract 235)
    PubMedGoogle Scholar
  • 119 Garabedian HD, Gold HK, Leinbach RC, Johns JA, Yasuda T, Kanke M, Collen D. Comparative properties of two clinical preparations of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction. J Am Coll Cardiol 1987; 9: 599-607
    CrossrefPubMedGoogle Scholar
  • 120 Rijken DC, Emeis JJ. Clearance of the heavy and light polypeptide chains of human tissue-type plasminogen activator in rats. Biochem J 1986; 238: 643-6
    CrossrefPubMedGoogle Scholar
  • 121 Korninger C, Stassen JM, Collen D. Turnover of human extrinsic (tissue-type) plasminogen activator in rabbits. Thromb Haemost 1981; 46: 658-61
    Article in Thieme ConnectPubMedGoogle Scholar
  • 122 Kuiper J, Otter M, Rijken DC, van Berkel TJC. Characterization of the interaction in vivo of tissue-type plasminogen activator with liver cells. J Biol Chem 1988; 263: 18220-4
    PubMedGoogle Scholar
  • 123 Morton PA, Owensby DA, Sobel BE, Schwartz AL. Catabolism of tissue-type plasminogen activator by the human hepatoma cell line Hep G2. Modulation by plasminogen activator inhibitor type 1. J Biol Chem 1989; 264: 7228-35
    PubMedGoogle Scholar
  • 124 Krause J, Seydel W, Heinzel G, Tanswell P. Different receptors mediate the hepatic catabolism of tissue-type plasminogen activator and urokinase. Biochem J 1990; 267: 647-52
    CrossrefPubMedGoogle Scholar
  • 125 Barnathan ES, Cines D, Barone K, Kuo A, Larsen GR. Differential binding of recombinant wild type and variant t-PA to human endothelial cells. Fibrinolysis 1988; 2 (Suppl 1) 28 (Abstract 58)
    PubMedGoogle Scholar
  • 126 Ramakrishnan V, Sinicropi DV, Dere R, Darbonne WC, Bechtol KB, Baker JB. Interaction of wild-type and catalytically inactive mutant forms of tissue-type plasminogen activator with human umbilical vein endothelial cell monolayers. J Biol Chem 1990; 265: 2755-62
    PubMedGoogle Scholar
  • 127 Russel ME, Quertermous T, Declerck PJ, Collen D, Haber E, Homcy CJ. Binding of tissue-type plasminogen activator with human endothelial cell monolayers. Characterization of the high affinity interaction with plasminogen activator inhibitor-1. J Biol Chem 1990; 265: 2569-75
    PubMedGoogle Scholar
  • 128 Larsen GR, Metzger M, Henson K, Blue Y, Horgan P. Pharmacokinetic and distribution analysis of variant forms of tissue-type plasminogen activator with prolonged clearance in rat. Blood 1989; 73: 1842-50
    PubMedGoogle Scholar
  • 129 Trill JJ, Fong KL, Shebuski RJ, McDevitt P, Rosa MD, Johanson K, Williams D, Boyle KE, Sellers TS, Reff ME. Expression and characterisation of finger protease (FP); a mutant tissue-type plasminogen activator (t-PA) with improved pharmacokinetics. Fibrinolysis 1990; 4: 131-40
    PubMedGoogle Scholar
  • 130 Browne MJ, Carey JE, Chapman CG, Tyrrell AWR, Entwisle C, Lawrence GMP, Dodd I, Esmail A, Robinson JH. A tissue-type plasminogen activator mutant with prolonged clearance in vivo. Effect of removal of the growth factor domain. J Biol Chem 1988; 263: 1599-602
    PubMedGoogle Scholar
  • 131 Sobel BE, Sarnoff SJ, Nachowiak DA. Augmented and sustained plasma concentrations after intramuscular injections of molecular variants and deglycosylated forms of tissue-type plasminogen activators. Circulation 1990; 81: 1362-73
    CrossrefPubMedGoogle Scholar
  • 132 Ahern TJ, Morris GE, Barone KM, Horgan PG, Timony GA, Angus LB, Henson KS, Stoudemire JB, Langer-Safer PR, Larsen GR. Site-directed mutagenesis in human tissue-plasminogen activator. J Biol Chem 1990; 265: 5540-5
    PubMedGoogle Scholar
  • 133 Browne MJ, Chapman CG, Dodd I, Esmail AF, Robinson JH. Deletion of a tripeptide sequence from the growth-factor domain of tissue-type plasminogen activator prolongs in vivo circulation. Thromb Res 1990; 59: 687-92
    CrossrefPubMedGoogle Scholar
  • 134 Lau D, Kuzma G, Wei CM, Livingston DJ, Hsiung N. A modified human tissue plasminogen activator with extended half-life in vivo. . Biotechnology 1987; 5: 953-8
    CrossrefPubMedGoogle Scholar
  • 135 Lau D, Kuzma G, Wei C-M, Livingston DJ, Hsiung N. Erratum. Biotechnology 1988; 6: 734
    PubMedGoogle Scholar
  • 136 Collen D, Stassen JM, Marafino B, Builder S, De Cock F, Ogez J, Tajiri D, Pennica D, Bennett WF, Salwa J, Hoyng CF. Biological properties of human tissue-type plasminogen activator obtained by expression of recombinant DNA in mammalian cells. J Pharmacol Exper Therap 1984; 231: 146-52
    PubMedGoogle Scholar
  • 137 Collen D, Stassen JM, Larsen G. Pharmacokinetics and thrombolytic properties of deletion mutants of human tissue-type plasminogen activator in rabbits. Blood 1988; 71: 216-9
    PubMedGoogle Scholar
  • 138 Cambier P, Van de Werf F, Larsen GR, Collen D. Pharmacokinetics and thrombolytic properties of a nonglycosylated mutant of human tissue-type plasminogen activator, lacking the finger and growth factor domains, in dogs with copper coil-induced coronary artery thrombosis. J Cardiovasc Pharmacol 1988; 11: 468-72
    CrossrefPubMedGoogle Scholar
  • 139 Martin U, Fischer S, Kohnert U, Lill H, Rudolph R, Sponer G, Stern A, Strein K. Thrombolytic. potency of an E. coli-produced novel variant of rt-PA in dogs. Fibrinolysis 1990; 4 (Suppl 3) 9 (Abstract 26)
    PubMedGoogle Scholar
  • 140 Gething M-J, Sambrook J, McGookey D. Addition of an oligosaccharide side-chain at an ectopic site on the EGF-like domain of t-PA prevents binding to specific receptors on hepatic cells. Thromb Haemost 1989; 62: 338 (Abstract 1051)
    PubMedGoogle Scholar
  • 141 Bernik MB, Oiler EP. Increased plasminogen activator (urokinase) in tissue culture after fibrin deposition. J Clin Invest 1973; 52: 823-34
    CrossrefPubMedGoogle Scholar
  • 142 Nolan C, Hall LS, Barlow GH, Tribby IIE. Plasminogen activator from human embryonic kidney cell cultures. Evidence for aproactivator. Biochim Biophys Acta 1977; 496: 384-400
    PubMedGoogle Scholar
  • 143 Husain SS, Gurewich V, Lipinski B. Purification and partial characterization of a single-chain high-molecular-weight form of urokinase from human urine. Arch Biochem Biophys 1983; 220: 31-8
    CrossrefPubMedGoogle Scholar
  • 144 Stump DC, Thienpont M, Collen D. Urokinase-related proteins in human urine. Isolation and characterization of single-chain urokinase (pro-urokinase) and urokinase-inhibitor complex. J Biol Chem 1986; 261: 1267-73
    PubMedGoogle Scholar
  • 145 Wun TC, Schleuning WD, Reich E. Isolation and characterization of urokinase from human plasma. J Biol Chem 1982; 257: 3276-83
    PubMedGoogle Scholar
  • 146 Wun TC, Ossowski L, Reich E. A proenzyme form of human urokinase. J Biol Chem 1982; 257: 7262-8
    PubMedGoogle Scholar
  • 147 Nielsen LS, Hansen JG, Skriver L, Wilson EL, Kaltoft K, Zeuthen J, Dano K. Purification of zymogen to plasminogen activator from human glioblastoma cells by affinity chromatography with monoclonal antibody. Biochemistry 1982; 21: 6410-5
    CrossrefPubMedGoogle Scholar
  • 148 Kohno T, Hopper P, Lillquist JS, Suddith RL, Greenlee R, Moir DT. Kidney plasminogen activator: a precursor form of human urokinase with high fibrin affinity. Biotechnology 1984; 2: 628-34
    CrossrefPubMedGoogle Scholar
  • 149 Sumi H, Maruyama M, Matsuo O, Mihara H, Toki N. Higher fibrin-binding and thrombolytic properties of single polypeptide chain-high molecular weight urokinase. Thromb Haemost 1982; 47: 29
    PubMedGoogle Scholar
  • 150 Sumi H, Kosugi T, Matsuo O, Mihara H. Physicochemical properties of highly purified kidney cultured plasminogen activator (single chain-urokinase). Acta Haematol Japan 1982; 45: 119-28
    PubMedGoogle Scholar
  • 151 Eaton DL, Scott RW, Baker JB. Purification of human fibroblast urokinase proenzyme and analysis of its regulation by proteases and protease nexin. J Biol Chem 1984; 259: 6241-7
    PubMedGoogle Scholar
  • 152 Kasai S, Arimura H, Nishida M, Suyama T. Proteolytic cleavage of single-chain pro-urokinase induces conformational change which follows activation of the zymogen and reduction of its high affinity for fibrin. J Biol Chem 1985; 260: 12377-81
    PubMedGoogle Scholar
  • 153 Stump DC, Lijnen HR, Collen D. Purification and characterization of single-chain urokinase-type plasminogen activator from human cell cultures. J Biol Chem 1986; 261: 1274-8
    PubMedGoogle Scholar
  • 154 Lijnen HR, Zamarron C, Blaber M, Winkler ME, Collen D. Activation of plasminogen by pro-urokinase. I. Mechanism. J Biol Chem 1986; 261: 1253-8
    PubMedGoogle Scholar
  • 155 Avgerinos GC, Drapeau D, Socolow JS, Mao J, Hsiao K, Broeze RJ. Spin filter perfusion system for high density cell culture: production of recombinant urinary type plasminogen activator in CHO cells. Bio/Technology 1990; 8: 54-8
    CrossrefPubMedGoogle Scholar
  • 156 Steffens GJ, Günzler WA, Ötting F, Frankus E, Flohe L. The complete amino acid sequence of low molecular mass urokinase from human urine. Hoppe-Seyler'Z Physiol Chem 1982; 363: 1043-58
    PubMedGoogle Scholar
  • 157 Günzler WA, Steffens GJ, Ötting F, Buse CT, Flohe L. Structural relationship between human high and low molecular mass urokinase. Hoppe-Seyler's Z Physiol Chem 1982; 363: 133-41
    PubMedGoogle Scholar
  • 158 Günzler WA, Steffens GJ, Ötting F, Kim SMA, Frankus E, Flohe L. The primary structure of high molecular mass urokinase from human urine. Hoppe-Seyler's Z Physiol Chem 1982; 363: 1155-65
    PubMedGoogle Scholar
  • 159 Stump DC, Lijnen HR, Collen D. Purification and characterization of a novel low molecular weight form of single-chain urokinase-type plasminogen activator. J Biol Chem 1986; 261: 17120-6
    PubMedGoogle Scholar
  • 160 Ichinose A, Fujikawa K, Suyama T. The activation of pro-urokinase by plasma kallikrein and its inactivation by thrombin. J Biol Chem 1986; 261: 3486-9
    PubMedGoogle Scholar
  • 161 Lijnen HR, Van Hoef B, Collen D. Activation with plasmin of two-chain urokinase-type plasminogen activator derived from single-chain urokinase-type plasminogen activator by treatment with thrombin. Eur J Biochem 1987; 169: 359-64
    CrossrefPubMedGoogle Scholar
  • 162 Melnick LM, Turner BG, Puma P, Price-Tillotson B, Salvato KA, Dumais DR, Moir DT, Broeze RJ, Avgerinos GC. Characterization of a nonglycosylated single chain urinary plasminogen activator secreted from yeast. J Biol Chem 1990; 265: 801-7
    PubMedGoogle Scholar
  • 163 Riccio A, Grimaldi G, Verde P, Sebastio G, Boast S, Blasi F. The human urokinase-plasminogen activator gene and its promoter. Nucleic Acids Res 1985; 13: 2759-71
    CrossrefPubMedGoogle Scholar
  • 164 Verde P, Stoppelli MP, Galeffi P, Di Nocera P, Blasi F. Identification and primary sequence of an unspliced human urokinase poly(A)+RNA. Proc Natl Acad Sci USA 1984; 81: 4727-31
    CrossrefPubMedGoogle Scholar
  • 165 Collen D, Zamarron C, Lijnen HR, Hoylaerts M. Activation of plasminogen by pro-urokinase. II. Kinetics. J Biol Chem 1986; 261: 1259-66
    PubMedGoogle Scholar
  • 166 Lijnen HR, Van Hoef B, Collen D. Comparative kinetic analysis of the activation of human plasminogen by natural and recombinant single-chain urokinase-type plasminogen activator. Biochim Biophys Acta 1986; 884: 402-8
    CrossrefPubMedGoogle Scholar
  • 167 Nelles L, Lijnen HR, Collen D, Holmes WE. Characterization of recombinant human single chain urokinase-type plasminogen activator mutants produced by site-specific mutagenesis of Lysine 158. J Biol Chem 1987; 262: 5682-9
    PubMedGoogle Scholar
  • 168 Lijnen HR, Van Hoef B, Nelles L, Holmes WE, Collen D. Enzymatic properties of single-chain and two-chain forms of a Lys158__Glu158 mutant of urokinase-type plasminogen activator. Eur J Biochem 1988; 172: 185-8
    CrossrefPubMedGoogle Scholar
  • 169 Ellis V, Scully MF, Kakkar VV. Plasminogen activation by single-chain urokinase in functional isolation. A kinetic study. J Biol Chem 1987; 262: 14998-5003
    PubMedGoogle Scholar
  • 170 Petersen LC, Lund LR, Nielsen LS, Dano K, Skriver L. One-chain urokinase-type plasminogen activator from human sarcoma cells is a proenzyme with little or no intrinsic activity. J Biol Chem 1988; 263: 11189-95
    PubMedGoogle Scholar
  • 171 Lijnen HR, Van Hoef B, Nelles L, Collen D. Plasminogen activation with single-chain urokinase-type plasminogen activator (scu-PA). Studies with active site mutagenized plasminogen (Ser740__Ala) and plasmin resistant scu-PA (Lys158__Glu). J Biol Chem 1990; 265: 5232-6
    PubMedGoogle Scholar
  • 172 Orfeo T, Shatos MA, Stump DC. Activation of plasminogen (Plg) by single-chain urokinase-type plasminogen activator (scu-PA): kinetic analysis in the presence of plasminogen activator inhibitor 1 (PAI-1). Fibrinolysis 1990; 4 (Suppl 3) 161 (Abstract 415)
    PubMedGoogle Scholar
  • 173 Lijnen HR, Nelles L, Van Hoef B, Demarsin E, Collen D. Structural and functional characterization of mutants of recombinant single-chain urokinase-type plasminogen activator obtained by site-specific mutagenesis of Lys158, Ile159 and Ile160. Eur J Biochem 1988; 177: 575-82
    CrossrefPubMedGoogle Scholar
  • 174 Vaughan D, Van Houtte E, Collen D. Urokinase binds to platelets through a specific saturable and low affinity mechanism. Fibrinolysis 1990; 4: 141-6
    PubMedGoogle Scholar
  • 175 Barnathan ES, Kuo A, Rosenfeld L, Kariko K, Leski M, Robbiati F, Nolli ML, Henkin J, Cines DB. Interaction of single-chain urokinase-type plasminogen activator with human endothelial cells. J Biol Chem 1990; 265: 2865-72
    PubMedGoogle Scholar
  • 176 Pannell R, Gurewich V. Pro-urokinase: a study of its stability in plasma and of a mechanism for its selective fibrinolytic effect. Blood 1986; 67: 1215-23
    PubMedGoogle Scholar
  • 177 Gurewich V. The sequential, complementary and synergistic activation of fibrin-bound plasminogen by tissue plasminogen activator and pro-urokinase. Fibrinolysis 1989; 3: 59-66
    PubMedGoogle Scholar
  • 178 Husain SS, Gurewich V, Lipinski B. Purification and partial characterization of a single-chain high-molecular-weight form of urokinase from human urine. Arch Biochem Biophys 1983; 220: 31-8
    CrossrefPubMedGoogle Scholar
  • 179 Lijnen HR, Van Hoef B, De Cock F, Collen D. The mechanism of plasminogen activation and fibrin dissolution by single chain urokinase-type plasminogen activator in a plasma milieu in vitro. . Blood 1989; 73: 1864-1872
    PubMedGoogle Scholar
  • 180 Claeys H, Vermylen J. Physicochemical and proenzyme properties of NH2-terminal glutamic acid and NH2-terminal lysine human plasminogen. Influence of 6-aminohexanoic acid. Biochim Biophys Acta 1974; 342: 351-9
    PubMedGoogle Scholar
  • 181 Declerck PJ, Lijnen HR, Verstreken M, Moreau H, Collen D. A monoclonal antibody specific for two chain urokinase-type plasminogen activator. Application to the study of the mechanism of clot lysis with single-chain urokinase-type plasminogen activator in plasma. Blood 1990; 75: 1794-800
    PubMedGoogle Scholar
  • 182 Collen D, Mao J, Stassen JM, Broeze R, Lijnen HR, Abercrombie D, Puma P, Almeda S, Vovis G. Thrombolytic properties of Lys-158 mutants of recombinant single chain urokinase-type plasminogen activator (scu-PA) in rabbits with jugular vein thrombosis. J Vasc Med Biol 1989; 1: 46-9
    PubMedGoogle Scholar
  • 183 Lijnen HR, Nelles L, Holmes W, Collen D. Biochemical and thrombolytic properties of a low molecular weight form (comprising Leu 144 through Leu411) of recombinant single-chain urokinase-type plasminogen activator. J Biol Chem 1988; 263: 5594-8
    PubMedGoogle Scholar
  • 184 Behrendt N, Ronne E, Ploug M, Petri T, Lober D, Nielsen LS, Schleuning WD, Blasi F, Dano K. The human receptor for urokinase plasminogen activator. J Biol Chem 1990; 265: 6453-60
    PubMedGoogle Scholar
  • 185 Barnathan ES, Kuo A, Kariko K, Rosenfeld L, Murray SC, Behrendt N, Ronne E, Weiner D, Henkin J, Cines DB. Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA. Blood 1990; 76: 1795-806
    PubMedGoogle Scholar
  • 186 Roldan AL, Cubellis MV, Masucci MT, Behrendt N, Lund LR, Dano K, Appella E, Blasi F. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J 1990; 9: 467-74
    PubMedGoogle Scholar
  • 187 Cubellis MV, Wun TC, Blasi F. Receptor-mediated internalization and degradation of urikinase is caused by its specific inhibitor PAI-1. EMBO J 1990; 9: 1079-85
    PubMedGoogle Scholar
  • 188 Vovis GP, Mao J, Broeze B, Abercrombie P, Puma P, Hsaio K, Almeda S. Amino acid changes at Lys-158 that alter the sensitivity of scu-PA to cleavage by plasmin. Thromb Haemost 1987; 58: 439 (Abstract 1618)
    Article in Thieme ConnectPubMedGoogle Scholar
  • 189 Gurewich V, Pannell R, Broeze RJ, Mao J. Characterization of the intrinsic fibrinolytic properties of pro-urokinase through a study of plasmin-resistant mutant forms produced by site-specific mutagenesis of lysine 158. J Clin Invest 1988; 82: 1956-62
    CrossrefPubMedGoogle Scholar
  • 190 Lijnen HR, Gheysen D, de Foresta F, Piérard L, Jacobs P, Bollen A, Collen D. Characterization of a mutant of recombinant human single-chain urokinase-type plasminogen activator (scu-PA) obtained by substitution of arginine156 and lysine 158 with threonine. Fibrinolysis 1988; 2: 85-93
    PubMedGoogle Scholar
  • 191 Eguchi Y, Sakata Y, Matsuda M, Osada H, Numao N, Ohmori M, Kondo K. Characterization of thrombin- and plasmin-resistant mutants of recombinant human single chain urokinase-type plasminogen activator. J Biochem 1990; 108: 72-9
    CrossrefPubMedGoogle Scholar
  • 192 Abercrombie DM, Buchinski B, Salvato KA, Vovis GF, Stump DC, Broeze RJ. Fibrin specific thrombolysis by two-chain urokinase-type plasminogen activator cleaved after arginine 156 by thrombin. Thromb Haemost 1990; 64: 426-32
    Article in Thieme ConnectPubMedGoogle Scholar
  • 193 Collen D, Dewerchin M, Stassen JM, Kieckens L, Lijnen HR. Thrombolytic and pharmacokinetic properties of conjugates of urokinase-type plasminogen activator with a monoclonal antibody specific for cross-linked fibrin. Fibrinolysis 1989; 3: 197-202
    PubMedGoogle Scholar
  • 194 Piérard L, Jacobs P, Gheysen D, Hoylaerts M, André B, Topisirovic L, Cravador A, de Foresta F, Herzog A, Collen D, De Wilde M, Bollen A. Mutant and chimeric recombinant plasminogen activators : Production in eukaryotic cells and preliminary characterization. J Biol Chem 1987; 262: 11771-8
    PubMedGoogle Scholar
  • 195 Gheysen D, Lijnen HR, Piérard L, de Foresta F, Demarsin E, Jacobs P, De Wilde M, Bollen A, Collen D. Characterization of a recombinant fusion protein of the finger domain of tissue-type plasminogen activator with a truncated single chain urokinase-type plasminogen activator. J Biol Chem 1987; 262: 11779-84
    PubMedGoogle Scholar
  • 196 de Vries C, Veerman H, Blasi F, Pannekoek H. Artificial exon shuffling between tissue-type plasminogen activator (t-PA) and urokinase (u-PA): a comparative study on the fibrinolytic properties of t-PA/u-PA hybrid proteins. Biochemistry 1988; 27: 2565-72
    CrossrefPubMedGoogle Scholar
  • 197 Lee SG, Kalyan N, Wilhelm J, Hum WT, Rappaport R, Cheng SM, Dheer S, Urbano C, Hartzell RW, Rochetti-Blume M, Levner M, Hung PP. Construction and expression of hybrid plasminogen activators prepared from tissue-type plasminogen activator and urokinase-type plasminogen activator genes. J Biol Chem 1988; 263: 2917-24
    PubMedGoogle Scholar
  • 198 Heim J, Asselbergs F, Buergi R, Chaudhuri B, Kuenzi M, Meyhack B, Rajput B, van Oostrum J. Chimeric recombinant plasminogen activators - Expression and characterization. Thromb Haemost 1989; 62: 337 (Abstract 1048)
    Article in Thieme ConnectPubMedGoogle Scholar
  • 199 Mao J, Puma P, Hsiao K, Salvato K, Hemmerdinger H, Capparell N, Broeze R. Characterization of truncated scu-PA derivatives. Fibrinolysis 1988; 2 (Suppl 1) 50 (Abstract 112)
    PubMedGoogle Scholar
  • 200 Pierard L, Quintana LG, Reff ME, Bollen A. Production in eukaryotic cells and characterization of four hybrids of tissue-type and urokinase-type plasminogen activators. DNA 1989; 8: 321-8
    CrossrefPubMedGoogle Scholar
  • 201 Lijnen HR, Piérard L, Reff ME, Gheysen D. Characterization of a chimaeric plasminogen activator obtained by insertion of the second kringle structure of tissue-type plasminogen activator (amino acids 173 through 262) between residues Asp130 and Ser139 of urokinase-type plasminogen activator. Thromb Res 1988; 52: 431-41
    CrossrefPubMedGoogle Scholar
  • 202 Nelles L, Lijnen HR, Collen D, Holmes WE. Characterization of a fusion protein consisting of amino acids 1 to 263 of tissue-type plasminogen activator and amino acids 144 to 411 of urokinase-type plasminogen activator. J Biol Chem 1987; 262: 10855-62
    PubMedGoogle Scholar
  • 203 Lijnen HR, Nelles L, Van Hoef B, Demarsin E, Collen D. Characterization of a chimeric plasminogen activator consisting of amino acids 1 to 274 of tissue-type plasminogen activator and amino acids 138 to 411 of single-chain urokinase-type plasminogen activator. J Biol Chem 1988; 263: 19083-91
    PubMedGoogle Scholar
  • 204 Collen D, Stassen JM, Demarsin E, Kieckens L, Lijnen HR, Nelles L. Pharmacokinetics and thrombolytic properties of chimaeric plasminogen activators consisting of the NH2-terminal region of human tissue-type plasminogen activator and the COOH-terminal region of human single chain urokinase-type plasminogen activator. J Vasc Med Biol 1989; 1: 234-40
    PubMedGoogle Scholar
  • 205 Nelles L, Lijnen HR, Van Nuffelen A, Demarsin E, Collen D. Characterization of domain deletion and/or duplication mutants of a recombinant chimera of tissue-type plasminogen activator and urokinase-type plasminogen activator (rt-PA/u-PA). Thromb Haemost 1990; 64: 53-60
    Article in Thieme ConnectPubMedGoogle Scholar
  • 206 Collen D, Lijnen HR, Nelles L, Stassen JM. Thrombolytic and pharmacokinetic properties of chimeric (tissue-type/urokinase-type) plasminogen activators. (Circulation, submitted)
    PubMedGoogle Scholar
  • 207 Robbins KC, Tanaka Y. Covalent molecular weight ~92000 hybrid plasminogen activator derived from human plasmin amino-terminal and urokinase carboxyl-terminal domains. Biochemistry 1986; 25: 3603-11
    CrossrefPubMedGoogle Scholar
  • 208 Robinson JH, Dodd I, Esmail A, Ferres H, Nunn B. Slow clearance of acylated, hybrid thrombolytic enzymes. Thromb Haemost 1988; 59: 421-5
    Article in Thieme ConnectPubMedGoogle Scholar
  • 209 Langer-Safer PR, Ahern TJ, Angus LB, Barone KM, Brenner MJ, Horgan PG, Morris GE, Stoudemire JB, Timony GA, Larsen GR. Replacement of finger and growth factor domains of tissue plasminogen activator with plasminogen kringle 1. Biochemical and pharmacological characterization of a novel chimera containing a high-affinity fibrin-binding domain linked to a heterologous protein. J Biol Chem 1991; 266: 3715-23
    PubMedGoogle Scholar
  • 210 Devlin JJ, Devlin PE, Clark R, O'Rourke EC, Levenson C, Mark DF. Novel expression of chimeric plasminogen activators in insect cells. Biotechnology 1989; 7: 286-92
    CrossrefPubMedGoogle Scholar
  • 211 Homandberg GA, Wai T. Insertion of fibrin peptides into urokinase enhances fibrin affinity. Thromb Res 1990; 58: 403-12
    CrossrefPubMedGoogle Scholar
  • 212 Fears R, Dodd I, Ferres H, Robinson JH. Kinetic studies on novel plasminogen activators. Biochem J 1990; 266: 693-6
    CrossrefPubMedGoogle Scholar
  • 213 Wilson S, Chamberlain P, Dodd I, Esmail A, Robinson JH. Interaction of a plasmin A-chain/t-PA B-chain hybrid enzyme with plasma inhibitors in vivo and in vitro. . Thromb Haemost 1990; 63: 459-63
    Article in Thieme ConnectPubMedGoogle Scholar
  • 214 Maksimenko AV, Torchilin VP. Water-soluble urokinase derivatives with increased affinity to the fibrin clot. Thromb Res 1985; 38: 289-95
    CrossrefPubMedGoogle Scholar
  • 215 Kobayashi Y, Watabe K, Mukohara Y, Satoh M, Nakamura H. Human prourokinase-like polypeptides and their preparation methods.. International Publication Number WO 90/15867
    PubMedGoogle Scholar
  • 216 Phillips DA, Fisher M, Smith TW, Davis MA, Pang RHL. The effects of a new tissue plasminogen activator analogue, FB-Fb-CF, on cerebral reperfusion in a rabbit embolic stroke model. Ann Neurol 1989; 25: 281-5
    CrossrefPubMedGoogle Scholar
  • 217 Morrison SL, Johnson MJ, Herzenberg LA, Oi VT. Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc Natl Acad Sci USA 1984; 81: 6851-5
    CrossrefPubMedGoogle Scholar
  • 218 Rodwell JD. Engineernig monoclonal antibodies. Nature 1989; 342: 99-100
    CrossrefPubMedGoogle Scholar
  • 219 Jones PT, Dear H, Foote J, Neuberger MS, Winter G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 1986; 321: 522-5
    CrossrefPubMedGoogle Scholar
  • 220 Bode C, Matsueda G, Hui KY, Haber E. Antibody-directed urokinase: A specific fibrinolytic agent. Science 1985; 229: 765-7
    CrossrefPubMedGoogle Scholar
  • 221 Haber E, Quertermous T, Matsueda GR, Runge MS. Innovative approaches to plasminogen activator therapy. Science 1989; 243: 51-6
    CrossrefPubMedGoogle Scholar
  • 222 Runge MS, Bode C, Matsueda GR, Haber E. Conjugation to an antifibrin monoclonal antibody enhances the fibrinolytic potency of tissue plasminogen activator in vitro. . Biochemistry 1988; 27: 1153-7
    CrossrefPubMedGoogle Scholar
  • 223 Runge MS, Bode C, Matsueda GR, Haber E. Antibody-enhanced thrombolysis: targeting of tissue plasminogen activator in vivo. . Proc Natl Acad Sci USA 1987; 84: 7659-62
    CrossrefPubMedGoogle Scholar
  • 224 Bode C, Runge MS, Newell JB, Matsueda GR, Haber E. Characterization of an antibody-urokinase conjugate. A plasminogen activator targeted to fibrin. J Biol Chem 1987; 262: 10819-23
    PubMedGoogle Scholar
  • 225 Bode C, Runge MS, Schönermark S, Eberle T, Newell JB, Kubler W, Haber E. Conjugation to antifibrin Fab' enhances fibrinolytic potency of single-chain urokinase plasminogen activator. Circulation 1990; 81: 1974-80
    CrossrefPubMedGoogle Scholar
  • 226 Bode C, Runge MS, Newell JB, Matsueda GR, Haber E. Thrombolysis by a fibrin-specific antibody Fab'-urokinase conjugate. J Mol Cell Cardiol 1987; 19: 335-41
    CrossrefPubMedGoogle Scholar
  • 227 Schnee JM, Runge MS, Matsueda GR, Hudson NW, Seidman JG, Haber E, Quertermous T. Construction and expression of a recombinant antibody-targeted plasminogen activator. Proc Natl Acad Sci 1987; 84: 6904-8
    CrossrefPubMedGoogle Scholar
  • 228 Runge MS, Huang P, Savard CE, Schnee JM, Love TW, Bode C, Matsueda GR, Haber E, Quertermous T. A recombinant molecule with antifibrin antibody and single-chain urokinase activities has increased fibrinolytic potency.. Circulation 1988; 78: II/509
    PubMedGoogle Scholar
  • 229 Dewerchin M, Lijnen HR, Van Hoef B, De Cock F, Collen D. Biochemical properties of conjugates of urokinase-type plasminogen activator with a monoclonal antibody specific for cross-linked fibrin. Eur J Biochem 1989; 185: 141-9
    CrossrefPubMedGoogle Scholar
  • 230 Lijnen HR, Dewerchin M, De Cock F, Collen D. Effect of fibrin-targeting on clot lysis with urokinase-type plasminogen activator. Thromb Res 1990; 57: 333-42
    CrossrefPubMedGoogle Scholar
  • 231 Dewerchin M, Lijnen HR, Collen D. Characterisation of a chemical conjugate between a low molecular weight form of recombinant single chain urokinase-type plasminogen activator (comprising Leu144 through Leu411) and F(ab')2-fragments of a fibrin D-dimer-specific monoclonal antibody. Fibrinolysis 1990; 4: 11-8
    PubMedGoogle Scholar
  • 232 Dewerchin M, Lijnen HR, Van Hoef B, De Cock F, Collen D. Characterisation of conjugates of thrombin-treated single-chain urokinase-type plasminogen activator with a monoclonal antibody specific for cross-linked fibrin. Fibrinolysis 1990; 4: 19-26
    PubMedGoogle Scholar
  • 233 Holvoet P, Laroche Y, Lijnen HR, Demarsin E, Mathijssens G, Collen D. Characterization of a single-chain recombinant plasminogen activator consisting of a Fv fragment derived from a D-dimer specific antibody and low molecular weight single-chain urokinase (rscu-PA-32k). Thromb Haemost (Abstract, submitted)
    PubMedGoogle Scholar
  • 234 Collen D, Dewerchin M, Rapold H, Lijnen HR, Stassen JM. Thrombolytic and pharmacokinetic properties of a conjugate of recombinant single-chain urokinase-type plasminogen activator with a monoclonal antibody specific for cross-linked fibrin in a baboon venous thrombosis model. Circulation 1990; 82: 1744-53
    CrossrefPubMedGoogle Scholar
  • 235 Loscalzo J, Vaughan DE. Tissue plasminogen activator promotes platelet disaggregation in plasma. J Clin Invest 1987; 79: 1749-55
    CrossrefPubMedGoogle Scholar
  • 236 Jang IK, Gold HK, Ziskind AA, Fallon JT, Holt RE, Leinbach RC, May JW, Collen D. Differential sensitivity of erythrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissue-type plasminogen activator. A possible explanation for resistance to coronary thrombolysis. Circulation 1989; 70: 920-8
    PubMedGoogle Scholar
  • 237 Julian D, Kübler W, Norris RM, Swan HJC, Collen D, Verstraete M. Thrombolysis in Cardiovascular Disease. New York, Marcel Dekker Inc: 1989
    Google Scholar
  • 238 Bode C, Meinhardt G, Runge MS, Eberle T, Schuler G, Kübler W, Haber E. Conjugation of urokinase to an antiplatelet antibody results in a more potent fibrinolytic agent. Thromb Haemost 1989; 62: 483 (Abstract 1514)
    PubMedGoogle Scholar
  • 239 Dewerchin M, Lijnen HR, Stassen JM, De Cock F, Quertermous T, Ginsberg MH, Plow EF, Collen D. Effect of chemical conjugation of recombinant single-chain urokinase-type plasminogen activator with monoclonal antiplatelet antibodies, on platelet aggregation and on plasma clot lysis in vitro and in vivo. . Blood (submitted)
    PubMedGoogle Scholar
  • 240 Charpie JR, Runge MS, Matsueda GR, Collen D, Haber E. Enhancement of fibrinolysis by single chain urokinase (scu-PA) with a bifunctional antibody having both fibrin and scu-PA specificities. Clinical Research 1988; 36: 436A (Abstract)
    PubMedGoogle Scholar
  • 241 Bode C, Runge MS, Branscomb EE, Newell JB, Matsueda GR, Haber E. Antibody-directed fibrinolysis. An antibody specific for both fibrin and tissue plasminogen activator. J Biol Chem 1989; 264: 944-8
    PubMedGoogle Scholar
  • 242 Charpie JR, Runge MS, Matsueda GR, Haber E. A bispecific antibody enhances the fibrinolytic potency of single-chain urokinase. Biochemistry 1990; 29: 6374-8
    CrossrefPubMedGoogle Scholar
  • 243 Branscomb EE, Runge MS, Savard CE, Adams KM, Matsueda GR, Haber E. Bispecific monoclonal antibodies produced by somatic cell fusion increase the potency of tissue plasminogen activator. Thromb Haemost 1990; 64: 260-6
    Article in Thieme ConnectPubMedGoogle Scholar
  • 244 Kurokawa T, Iwasa S, Kakinuma A. Enhanced fibrinolysis by a bispecific monoclonal antibody reactive to fibrin and tissue plasminogen activator. Biotechnology 1989; 7: 1163-7
    CrossrefPubMedGoogle Scholar
  • 245 Kurokawa T, Iwasa S, Kakinuma A. Enhancement of fibrinolysis by bispecific monoclonal antibodies reactive to fibrin and plasminogen activators. Thromb Res 1990; Suppl X: 83-9
    PubMedGoogle Scholar
  • 246 Kurokawa T, Iwasa S, Kakinuma A, Stassen JM, Lijnen HR, Collen D. Enhancement of clot lysis in vitro and in vivo with a bispecific monoclonal antibody directed against human fibrin and against urokinase-type plasminogen activator.. Thromb Haemost (submitted)
    PubMedGoogle Scholar