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Insight into the structure, function, and biosynthesis of factor VIII through recombinant DNA technology

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References

  1. Addis T (1911) The pathogenesis of hereditary hemophilia. J Pathol Bacteriol 15: 452

    Google Scholar 

  2. Andersson L-O, Brown JE (1981) Interaction of factor VIII-von Willebrand factor with phospholipid vesicles. Biochem J 200: 161–167

    Google Scholar 

  3. Bauer KA, Kass BL, Cate H ten, Bednarek MA, Hawiger JJ, Rosenberg D (1989) Detection of factor X activation in humans. Blood 74: 2007–2015

    Google Scholar 

  4. Bauer KA, Kass BL, Cate H ten, Rosenberg RD (1989) Factor IX is activated in vivo by the tissue factor mechanism. Blood 76: 731–736

    Google Scholar 

  5. Bertina RM, Broekmans AW, Linden IK van der, Mertens K (1982) Protein C deficiency in a Dutch family with thrombolic disease. Thromb Haemost 48: 1–5

    Google Scholar 

  6. Bevers EM, Comfurius P, Van Rijn JLML, Hemker HC, Zwaal RFA (1982) Generation of prothrombin-converting activity and the exposure of phosphatidylserine at the outer surface of platelets. Eur J Biochem 122: 429–436

    Google Scholar 

  7. Bontempo EA, Lewis JH, Gorenc TJ (1987) Liver transplantation in hemophilia A. Blood 69: 1721–1724

    Google Scholar 

  8. Brinkhous KM, Sandberg H, Garris JB (1985) Purified human factor VIII procoagulant protein: comparative hemostasis response after infusions into hemophilic and von Willebrand disease dogs. Proc Natl Acad Sci USA 82: 8752–8756

    Google Scholar 

  9. Broze GJ Jr, Warren LA, Novotny WF (1988) The lipoproteinassociated coagulation inhibitor that inhibits the factor VIII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action. Blood 71: 335–343

    Google Scholar 

  10. Chang SC, Wooden SK, Nakaki T, Kim TK, Lin AY, Kung L, Attenello JW, Lee AS (1987) Rat gene encoding the 78-kDa glucose-regulated protein GRP78: its regulatory sequences and the effect of protein glycosylation on its expression. Proc Natl Acad Sci USA 84: 680–684

    Google Scholar 

  11. Dieijen G van, Tans G, Rosing J, Hemker HC (1981) The role of phospholipid and factor Villa in the activation of bovine factor X. J Biol Chem 256: 3433–3441

    Google Scholar 

  12. Dorner AJ, Bole DG, Kaufman RJ (1987) The relationship of N-linked glycosylation and heavy chain-binding protein association with the secretion of glycoproteins. J Cell Biol 105: 2665–2674

    Google Scholar 

  13. Dorner AJ, Krane MAG, Kaufman RJ (1988) Reduction of endogenous GRP78 levels improves secretion of a heterologous protein in CHO cells. Mol Cell Biol 8: 4063–4070

    Google Scholar 

  14. Dorner AJ, Wasley LC, Kaufman RJ (1989) Increased synthesis of secreted proteins induces expression of glucose-regulated proteins in butyrate-treated Chinese hamster ovary cells. J Biol Chem 264: 20602–20607

    Google Scholar 

  15. Dorner AJ, Wasley LC, Kaufman RJ (1990) Protein dissociation from GRP78 and secretion are blocked by depletion of cellular ATP levels. Proc Natl Acad Sci USA 87: 7429–7432

    Google Scholar 

  16. Douglas AS (1958) Antihemophilic globulin assay following plasma infusions in hemophilia. J Lab Clin Med 51: 850–859

    Google Scholar 

  17. Eaton D, Rodriguez H, Vehar GA (1986) Proteolytic processing of human factor VIII. Correlation of specific cleavages by thrombin, factor Xa, and activated protein C with activation and inactivation of factor VIII coagulant activity. Biochemistry 25: 505–512

    Google Scholar 

  18. Eaton DL, Wood WI, Eaton D, Hass PE, Hollingshead P, Wion K, Mather J, Lawn RM, Vehar GA, Gorman C (1987) Construction and characterization of an active factor VIII variant lacking the central one-third of the mulecule. Biochemistry 25: 8342–8347

    Google Scholar 

  19. Eaton DL, Hass PE, Riddle L, Mather J, Wiebe M, Gregory T, Vehar GA (1987) Characterization of recombinant human factor VIII. J Biol Chem 252: 3285–3290

    Google Scholar 

  20. Ezban M, Nordfang O (1986) Interaction of isolated heavy and light chains of factor VIII:C with the von Willebrand factor (abstract). Res Clin Lab 16: 112a

    Google Scholar 

  21. Fass DN, Knutson GJ, Katzmann JA (1982) Monoclonal antibodies to porcine factor VIII coagulant and their use in the isolation of active coagulant protein. Blood 59: 594–600

    Google Scholar 

  22. Fay PJ (1987) Subunit structure of thrombin-activated human factor Villa. Biochim Biophys Acta 952: 181–190

    Google Scholar 

  23. Fay PJ (1988) Reconstruction of human factor VIII from isolated subunits. Arch Biochem Biophys 252: 525–553

    Google Scholar 

  24. Fay PJ, Anderson MT, Chavin SI, Marder VJ (1986) The size of human factor VIII heterodimers and the effects produced by thrombin. Biochim Biophys Acta 871: 268–278

    Google Scholar 

  25. Foster PA, Fulcher CA, Marti T, Titani K, Zimmerman TS (1987) A major factor VIII binding domain resides within the amino-terminal 272 amino acid residues of von Willebrand factor. J Biol Chem 262: 8443–8446

    Google Scholar 

  26. Foster PA, Fulcher CA, Houghten RA, Zimmerman TS (1988) An immunogenic region within amino acid residues Val1670-Glu1684 of the factor VIII light chain induces antibodies which inhibit binding of factor VIII to von Willebrand factor. J Biol Chem 263: 5230–5234

    Google Scholar 

  27. Francis RT, McDonagh J, Mann KG (1986) Factor V is a substrate for the transamidase factor XIIIa. J Biol Chem 261: 9787–9792

    Google Scholar 

  28. Fulcher CA, Zimmerman TS (1982) Characterization of the human factor VIII procoagulant protein with a heterologous precipitating antibody. Proc Natl Acad Sci USA 79: 1648–1652

    Google Scholar 

  29. Fulcher CA, Roberts JR, Zimmerman TS (1983) Thrombin proteolysis of purified factor VIII. Correlation of activation with generation of a specific polypeptide. Blood 61: 807–811

    Google Scholar 

  30. Fulcher CA, Gardiner JE, Griffin JH, Zimmerman TS (1984) Proteolytic inactivation of human factor VIII procoagulant protein by activated protein C and its analogy with factor V. Blood 63: 486–489

    Google Scholar 

  31. Giles AR, Tinlin S, Greewood R (1982) A canine model of hemophilic (factor VIII:C deficiency) bleeding. Blood 60: 727–730

    Google Scholar 

  32. Gitschier J, Kogan S, Levinson B, Tuddenham EGD (1988) Mutations of factor VIII cleavage sites in hemophilia A. Blood 72: 1022–1028

    Google Scholar 

  33. Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C (1981) Deficiency of protein C in congenital thrombolic disease. J Clin Invest 68: 1370–1373

    Google Scholar 

  34. Hamer RJ, Koedam JA, Beeser-Visser NH, Sixma JJ (1987) The effect of thrombin on the complex between factor VIII and von Willebrand factor. Eur J Biochem 167: 253–259

    Google Scholar 

  35. Hamer RJ, Koedam JA, Beeser-Visser NH, Bertina RM, Mourik JA van, Sixma JJ (1987) Factor VIII binds to von Willebrand factor via its Mr-80,000 light chain. Eur J Biochem 166: 37–43

    Google Scholar 

  36. Hill-Eubanks DC, Parker CG, Lollar P (1989) Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin. Proc Natl Acad Sci USA 86: 6508–6512

    Google Scholar 

  37. Hultin MB, Jesty J (1981) The activation and inactivation of human factor VIII by thrombin: effect of inhibitors of thrombin. Activation and inactivation of human factor VIII. Blood 57: 476–482

    Google Scholar 

  38. Husten EJ, Esmon CT, Johnson AE (1987) The active site of blood coagulation factor Xa. Its distance from the phospholipid surface and its conformational sensitivity to components of the prothrombinase complex. J Biol Chem 262: 12953–12961

    Google Scholar 

  39. Israel DI, Kaufman RJ (1990) Retroviral-mediated transfer and amplification of a functional human factor VIII gene. Blood 75: 1074–1080

    Google Scholar 

  40. Kane WH, Lindhout MJ, Jackson CM, Majerus PW (1980) Factor Va-dependent binding of factor Xa to human platelets. J Biol Chem 255: 1170–1174

    Google Scholar 

  41. Kane WH, Davie EW (1988) Blood coagulation factors V and VIII: structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders. Blood 71: 359–555

    Google Scholar 

  42. Kassenbrock CK, Kelly RI (1989) Interaction of heavy chain binding protein (BiP/GRP78) with adenine nucleotides. EMBO J 8: 1461–1467

    Google Scholar 

  43. Kaufman RJ, Wasley LC, Spiliotes AJ, Gossels SD, Latt SA, Larsen GR, Kay RM (1985) Coamplification and coexpression of human tissue-type plasminogen activator and murine dihydrofolate reductase sequences in Chinese hamster ovary cells. Mol Cell Biol 5: 1750–1759

    Google Scholar 

  44. Kaufman RJ, Wasley LC, Furie BC, Furie B, Shoemaker C (1986) Expression, purification, and characterization of recombinant γ-carboxylated factor IX synthesized in Chinese hamster ovary cells. J Biol Chem 261: 9622–9628

    Google Scholar 

  45. Kaufman RJ, Pittman DD, Wasley LC, Foster BW, Amphlett GW, Giles AR (1987) Directed mutagenesis in the study of the requirements for factor VIII activity in vitro and in vivo (abstract). Thromb Haemost 58: 1970a

    Google Scholar 

  46. Kaufman RJ, Wasley LC, Dorner AJ (1988) Synthesis, processing and secretion of recombinant human factor VIII expressed in mammalian cells. J Biol Chem 263: 6352–6362

    Google Scholar 

  47. Kaufman RJ, Wasley LC, Davies MV, Wise RJ, Israel DI, Dorner AJ (1989) Effect of von Willebrand factor coexpression on the synthesis and secretion of factor VIII in Chinese hamster ovary cells. Mol Cell Biol 9: 1233–1242

    Google Scholar 

  48. Kelly DA, Summerfield JA, Tuddenham EGD (1984) Localization of factor VIII C: antigen in guinea-pig tissues and isolated liver cell fractions. Br J Haematol 56: 535–543

    Google Scholar 

  49. Koedam JA (1989) Interaction between factor VIII and von Willebrand factor. PhD Thesis, University of Utrecht

  50. Koedam JA, Meijers JCM, Sixma JJ, Bouma BN (1988) Inactivation of human factor VIII by activated protein C cofactor activity of protein S and protective effect of von Willebrand factor. J Clin Invest 82: 1236–1243

    Google Scholar 

  51. Kozutsumi Y, Segal SK, Normington K, Gething M-J, Sambrook J (1988) The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 332: 462–464

    Google Scholar 

  52. Lajmonovich A, Hudry-Clergeon G, Freyssinet J-M, Marguerie G (1981) Human factor VIII procoagulant activity and phospholipid interaction. Biochim Biophys Acta 678: 123–136

    Google Scholar 

  53. Lane S (1840) Haemorrhagic diathesis. Successful transfusion of blood. Lancet I: 185–188

    Google Scholar 

  54. Lewis JH, Bontempo FA, Sperio JA (1985) Liver transplantation in a hemophiliac. N Engl J Med 312: 1189–1190

    Google Scholar 

  55. Leyte A, Verbeet MP, Brodneiwicz-Proba T (1989) The interaction between human blood-coagulation factor VIII and von Willebrand factor: characterization of a high-affinity binding site on factor VIII. Biochem J 257: 679–683

    Google Scholar 

  56. Lollar P, Parker CG (1987) Stoichiometry of the porcine factor VIII-von Willebrand factor association. J Biol Chem 262: 17272–17576

    Google Scholar 

  57. Lollar P, Parker CG (1989) Subunit structure of thrombin-activated porcine factor VIII. Biochemistry 28: 666–674

    Google Scholar 

  58. Lollar P, Knutson GJ, Fass DN (1984) Stabilization of thrombin-activated porcine factor VIII:C by factor IXa and phospholipid. Blood 63: 1303–1308

    Google Scholar 

  59. Lollar P, Hill-Eubanks DC, Parker CG (1988) Association of the factor VIII light chain with von Willebrand factor. J Biol Chem 263: 10451–10455

    Google Scholar 

  60. Machamer CE, Doms RW, Bole DG, Helenius A, Rose JK (1990) Heavy-chain binding-protein recognizes incompletely disulphide-bonded forms of vesicular stomatitis virus G protein. J Biol Chem 265: 6879–6883

    Google Scholar 

  61. Mann KG, Jenny RJ, Krishnaswamy S (1988) Cofactor proteins in the assembly and expression of blood clotting enzyme complexes. Ann Rev Biochem 57: 915–956

    Google Scholar 

  62. Marchioro TL, Hougie C, Ragde H (1969) Hemophilia: role of organ homografts. Science 163: 188–190

    Google Scholar 

  63. Mikkelsen J, Thomsen J, Kongerslev L, Christensen M, Ezban M (1989) Heterogeneity in the tyrosine sulfation of Chinese hamster ovary cell produced recombinant FVIII (abstract). Thromb Haemost 62: 594a

    Google Scholar 

  64. Miletich JP, Jackson CM, Majerus PW (1978) Properties of the factor Xa binding site on human platelets. J Biol Chem 253: 6908–6916

    Google Scholar 

  65. Munro S, Pelham HRB (1986) An Hsp70-like protein in the ER: identity with the 78 Kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 46: 291–300

    Google Scholar 

  66. Nesheim ME, Pittman DD, Wang JH, Slonosky D, Giles AR, Kaufman RJ (1988) The binding of35S-labeled recombinant factor VIII to activated and unactivated human platelets. J Biol Chem 263: 16467–16470

    Google Scholar 

  67. Nesheim M, Pittman DD, Fass DN (1991) The effect of von Willebrand factor on the binding of factor VIII to thrombin activated platelets. J Biol Chem (in press)

  68. Ng DTW, Randall RE, Lamb RA (1989) Intracellular maturation and transport of the SV5 type II glycoprotein hemagglutinin-neuraminidase: specific and transient association with GRP78-BiP in the endoplasmic reticulum and extensive internalization from the cell surface. J Cell Ciol 109: 3273–3289

    Google Scholar 

  69. Nordfang O, Ezban M (1988) Generation of active coagulation factor VIII from isolated subunits. J Biol Chem 263: 1115–1118

    Google Scholar 

  70. O'Brien DP, Tuddenham EGD (1989) Purification and characterization of factor VIII 1,689-Cys: a nonfunctional cofactor occurring in a patient with severe hemophilia A. Blood 73: 2117–2122

    Google Scholar 

  71. Otto JE (1803) An account of an hemorrhagic disposition existing in certain families. Med Repository 6: 1

    Google Scholar 

  72. Over J, Sixma JJ, Doucet-de-Bruine MHM (1978) Survival of125iodine-labeled factor VIII in normals and patients with classic hemophilia. J Clin Invest 62: 223–234

    Google Scholar 

  73. Patek AJ Jr, Taylor FHL (1937) Hemophilia: II. Some properties of a substance obtained from normal human plasma effective in accelerating the coagulation in hemophilic blood. J Clin Invest 16: 113–124

    Google Scholar 

  74. Pittman DD, Kaufman RJ (1988) Proteolytic requirements for thrombin activation of anti-hemophilic factor (factor VIII). Proc Natl Acad Sci USA 85: 2429–2433

    Google Scholar 

  75. Pittman DD, Kaufman RJ (1989) Structure-function relationships of factor VIII elucidated through recombinant DNA technology. Thromb Haemost 61: 161–165

    Google Scholar 

  76. Pittman DD, Wasley LC, Murray BL, Wang JH, Kaufman RJ (1987) Analysis of structural requirements for factor VIII function using site-directed mutagenesis (abstract). Thromb Haemost 58: 804a

    Google Scholar 

  77. Poole S, Firtel RA, Lamar E, Rowekamp W (1981) Sequence and expression of the Discoidin I gene family inDictyostelium discoideum. J Mol Biol 153: 273–289

    Google Scholar 

  78. Rao LVM, Rapaport SI (1987) Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation. Blood 69: 645–651

    Google Scholar 

  79. Rick ME, Hoyer LW (1977) Thrombin activation of factor VIII: the effect of inhibitors. Br J Haematol 36: 585–597

    Google Scholar 

  80. Rosner F (1969) Hemophilia in the Talmud and rabbinic writings. Ann Intern Med 70: 833–837

    Google Scholar 

  81. Rotblat F, O'Brien DP, O'Brien FJ, Goodall AH, Tuddenham EGD (1985) Purification of human factor VIII:C and its characterization by Western blotting using monoclonal antibodies. Biochemistry 24: 4294–4300

    Google Scholar 

  82. Sewerin KI, Larsen K, Sandberg H, Andersson L-O (1986) The binding between factor VIII and von Willebrand factor (abstract). Res Clin Lab 16: 235a

    Google Scholar 

  83. Takahashi Y, Kalafatis M, Girma J-P, Swerin K, Andersson L-O, Meyer D (1987) Localization of factor VIII binding domain on a 34 kilodalton fragment of the N-terminal portion of von Willebrand factor. Blood 70: 1679–1682

    Google Scholar 

  84. Toole JJ, Knopf JL, Wozney JM (1984) Molecular cloning of a cDNA encoding human antihemophilic factor. Nature 312: 342–347

    Google Scholar 

  85. Toole JJ, Pittman DD, Orr EC, Murtha P, Wasley LC, Kaufman RJ (1986) A large region (= 95 kDa) of human factor VIII is dispensable for in vitro procoagulant activity. Proc Natl Acad Sci USA 83: 5939–5942

    Google Scholar 

  86. Tracy PB, NeSheim ME, Mann KG (1981) Coordinate binding of factor-Va to the unstimulated platelet. J Biol Chem 256: 743–751

    Google Scholar 

  87. Tuddenham EGD, Lane RS, Rotblat F (1982) Response to infusions of polyelectrolyte fractionated human factor VIII concentrate in human hemophilia A and von Willebrand's disease. Br J Haematol 52: 259–267

    Google Scholar 

  88. Vehar GA, Keyt B, Eaton D (1984) Structure of human factor-VIII. Nature 312: 337–342

    Google Scholar 

  89. Walker FJ, Chavin SI, Fay PJ (1987) Inactivation of factor VIII by activated protein C and protein S. Arch Biochem Biophys 252: 322–328

    Google Scholar 

  90. Wasley LC, Atha DH, Bauer KA, Kaufman RJ (1987) Expression and characterization of human antithrombin III synthesized in mammalian cells. J Ciol Chem 262: 14766–14772

    Google Scholar 

  91. Watowich SS, Morimoto RI (1988) Complex regulation of heat shock- and glucose-responsive genes in human cells. Mol Cell Biol 8: 393–405

    Google Scholar 

  92. Webster WP, Zukoski CF, Hutchin P, Reddick RL, Mandel SR, Penick GD (1971) Plasma factor VIII synthesis and control as revealed by canine organ transplantation. Am J Physiol 220: 1147–1154

    Google Scholar 

  93. Weiss HJ, Sussman II, Hoyer LW (1977) Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand's disease. J Clin Invest 60: 390–404

    Google Scholar 

  94. White GC, McMillan CW, Kingdon HS, Shoemaker CB (1989) Use of recombinant antihemophilic factor in the treatment of two patients with classic hemophilia. N Engl J Med 320: 166–170

    Google Scholar 

  95. Wion KL, Kelly D, Summerfield JA (1985) Distribution of factor VIII mRNA and antigen in human liver and other tissues. Nature 317: 726–729

    Google Scholar 

  96. Wood WT, Capon DJ, Simonsen CC (1984) Expression of active human factor VIII from recombinant DNA clones. Nature 312: 330–337

    Google Scholar 

  97. Zelechowska MG, Mourik JA van, Brodniewicz-Proba T (1985) Ultrastructural localization of factor VIII procoagulant antigen in human liver hepatocytes. Nature 317: 729–730

    Google Scholar 

  98. Zwaal RFA (1978) Membrane and lipid involvement in blood coagulation. Biochim Biophys Acta 515: 163–205

    Google Scholar 

  99. Fay PJ, Haidaris PJ, Smudzin TM (1991) Human factor VIIIa Subunit structure. J Biol Chem 266: 8957–8962

    Google Scholar 

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Kaufman, R.J. Insight into the structure, function, and biosynthesis of factor VIII through recombinant DNA technology. Ann Hematol 63, 155–165 (1991). https://doi.org/10.1007/BF01703248

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