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Thromb Haemost 1989; 61(02): 161-165
DOI: 10.1055/s-0038-1646551
Review Article
Schattauer GmbH Stuttgart

Structure-Function Relationships of Factor VIII Elucidated through Recombinant DNA Technology

Debra D Pittman
The Genetics Institute, Cambridge, MA, USA
,
Randal J Kaufman
The Genetics Institute, Cambridge, MA, USA
› Author Affiliations
Further Information

Publication History

Received 26 September 1988

Accepted after revision 30 December 1988

Publication Date:
30 June 2018 (online)

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Keywords

Hemophilia A - Site-directed mutagenesis - Coagulation - Hemostasis
 

  • References

  • 1 Sadler JE, Davie EW. Hemophilia A, hemophilia B and von Willebrand’s disease. In: Nienhuis AW, Leder P, Majerus PW. (eds) The Molecular Basis of Blood Diseases. WB Saunders Co; 1987. pp 575-630
    Search in Google Scholar
  • 2 van Dieijen G, Tans G, Rosing J, Hemker HC. The role of phospholipid and factor VIIIain the activation of bovine factor X. J Biol Chem 1981; 256: 3433-3441
    PubMedSearch in Google Scholar
  • 3 Vehar GA, Keyt B, Eaton D, Rodriquez H, O’Brien DP, Rotblat F, Oppermann H, Keck R, Wood WI, Harkins RW, Tuddenham EG D, Lawn RM, Capon DJ. Structure of human factor VIII. Nature (London) 1984; 312: 337-342
    CrossrefPubMedSearch in Google Scholar
  • 4 Wood WT, Capon DJ, Simonsen CC, Eaton DL, Gitschier J, Keyt B, Seeburg PH, Smith DH, Hillingshead P, Wion KL, Delwart E, Tuddenham EG D, Vehar GA, Lawn RM. Expression of active human factor VIII from recombinant DNA clones. Nature (London) 1984; 312: 330-337
    CrossrefPubMedSearch in Google Scholar
  • 5 Toole JJ, Knopf JL, Wozney JM, Sultzman LA, Beucker J, Pittman DD, Kaufman RJ, Brown E, Shoemaker C, Orr EC, Amphlett GW, Foster WB, Coe ML, Knutson GJ, Fass DN, Hewick RM. Molecular cloning of a cDNA encoding human antihemophilic factor. Nature 1986; 312: 342-347
    PubMedSearch in Google Scholar
  • 6 Poole S, Firtel RA, Lamar E, Rowekamp W. Sequence and expression of the Discoidin I gene family in dictyostelium discoideum. J Mol Biol 1981; 153: 273-289
    CrossrefPubMedSearch in Google Scholar
  • 7 Mann KG, Jenny RJ, Krishnaswamy S. Cofactor proteins in the assembly and expression of blood clotting enzyme complexes. Ann u Rev Biochem 1988; 57: 915-956
    PubMedSearch in Google Scholar
  • 8 Kane WH, Davie EW. Blood coagulation factors V and VIII: Structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders. Blood 1988; 71: 539-555
    PubMedSearch in Google Scholar
  • 9 Bontempo FA, Lewis JH, Gorenc TJ, Spero JA, Ragni MV, Scott JP, Starzl TE. Liver transplantation in hemophilia A. Blood 1987; 69: 1721-1724
    PubMedSearch in Google Scholar
  • 10 Zelechowska MG, van Mourik JA, Brodniewicz-Proba T. Ultrastructural localization of factor VIII procoagulant antigen in human liver hepatocytes. Nature 1985; 217: 729-730
    PubMedSearch in Google Scholar
  • 11 Wion KL, Kelley D, Summerfield JA, Tuddenham EG D, Lawn RM. Distribution fo factor VIII mRNA and antigen in human liver and other tissues. Nature 1985; 317: 726-729
    CrossrefPubMedSearch in Google Scholar
  • 12 Kaufman RJ, Wasley LC, Dorner AJ. Synthesis, processing, and secretion of recombinant human factor VIII expressed in mammalian cells. J Biol Chem 1988; 263: 6352-6362
    PubMedSearch in Google Scholar
  • 13 Munro S, Pelham HR B. An Hsp70-like protein in the ER: Identity with the 78 Kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 1986; 46: 291-300
    CrossrefPubMedSearch in Google Scholar
  • 14 Dorner AJ, Bole DG, Kaufman RJ. The relationship of N-linked glycosylation and heavy chain-binding protein association with the secretion of glycoproteins. J Cell Biol 1987; 105: 2665-2674
    CrossrefPubMedSearch in Google Scholar
  • 15 Tuddenham EG D, Lane RS, Rotblat F, Johnson AJ, Snape TJ, Middleton S, Kemoff PB A. Response to infusions of poly electrolyte fractionated hunian factor VIII concentrate in human hemophilia A and von Willebrand’s disease. Br J Haematol 1982; 52: 259-267
    CrossrefPubMedSearch in Google Scholar
  • 16 Weiss HJ, Sussman II, Hoyer LW. 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 1977; 60: 390-404
    CrossrefPubMedSearch in Google Scholar
  • 17 Brinkhous KM, Sandberg H, Garris JB, Mattsson C, Palm M, Griggs T, Read MS. Purified human factor VIII procoagulant protein: Comparatiive hemostatic response after infusions into hemophilic and von Willebrand disease dogs. Proc Natl Acad Sci (USA) 1985; 82: 8752-8756
    CrossrefPubMedSearch in Google Scholar
  • 18 Toole JJ, Pittman DD, Orr EC, Murtha P, Wasley LC, Kaufman RJ. A large region (= 95 kDa) of human factor VIII is dispensable for in vitro procoagulant activity. Proc Natl Acad Sci (USA) 1986; 83: 5939-5942
    CrossrefPubMedSearch in Google Scholar
  • 19 Eaton DL, Wood WI, Eaton D, Hass PE, Hollingshead P, Wion K, Mather J, Lawn RM, Vehar GA, Gorman C. Construction and characterization of an active factor VIII variant lacking the central one-third of the molecule. Biochemistry 1986; 25: 8342-8347
    PubMedSearch in Google Scholar
  • 20 Kaufman RJ, Pittman DD, Wasley LC, Foster BW, Amphlett GW, Giles AR. Directed mutagenesis in the study of the requirements for factor VIII activity in vitro and in vivo. Thromb Haemostas 1987; 58: 537 (Abstr 1970)
    PubMedSearch in Google Scholar
  • 21 Giles AR, Tinlin S, Greenwood R. A canine model of hemophilic (factor VIII:C deficiency) bleeding. Blood 1982; 60: 727-730
    PubMedSearch in Google Scholar
  • 22 Francis RT, McDonagh J, Mann KG. Factor V is a substrate for the transamidase factor XHIa. J Biol Chem 1986; 261: 9787-9792
    PubMedSearch in Google Scholar
  • 23 Eaton DL, Rodriguez HR, Vehar GA. 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 1986; 25: 505-512
    CrossrefPubMedSearch in Google Scholar
  • 24 Fulcher CA, Roberts JR, Zimmerman TS. Thrombin proteolysis of purified factor VIII procoagulant protein: Correlation of activation with generation of a specific polypeptide. Blood 1983; 61: 807-811
    PubMedSearch in Google Scholar
  • 25 Fay PJ, Anderson MT, Chavin SI, Marder VJ. The size of human factor VIII heterodimers and the effects produced by thrombin. Biochim Biophys Acta 1986; 871: 268-278
    CrossrefPubMedSearch in Google Scholar
  • 26 Rotblat F, O’Brien DP, O’Brien FJ, Goodall AH, Tuddenham EG D. Purification of human factor VIII:C and its characterization by Western blotting using monoclonal antibodies. Biochemistry 1985; 24: 4294-4300
    CrossrefPubMedSearch in Google Scholar
  • 27 Pittman DD, Kaufman RJ. Proteolytic requirements for thrombin activation of anti-hemophilic factor (factor VIII). Proc Natl Acad Sci (USA) 1988; 85: 2429-2433
    CrossrefPubMedSearch in Google Scholar
  • 28 Ware J, Toomey J, Fulcher C, Zimmerman TS, Stafford DW. Factor VIII:C antigenic determinants defined by recombinant DNA. Blood 1987; 70: 1440
    PubMedSearch in Google Scholar
  • 29 Scandella D, deGaaf Mahoney S, Mattingly M, Roeder D, Timmons L, Fulcher CA. Epitope mapping of human factor VIII inhibitor antibodies by deletion analysis of factor VIII fragments expressed in Escherichia coli. Proc Natl Acad Sci (USA) 1988; 85: 6152-6156
    CrossrefPubMedSearch in Google Scholar
  • 30 Lollar P, Hill-Eubanks DC, Parker CG. Association of the factor VIII light chain with von Willebrand factor. J Biol Chem 1988; 263: 10451-10455
    PubMedSearch in Google Scholar
  • 31 Gitschier J, Kogan S, Levinson B, Tuddenham EG D. Mutations of factor VIII cleavage sites in hemophilia A. Blood 1988; 72: 1022-1028
    PubMedSearch in Google Scholar
  • 32 Hultin MB, Jesty J. The activation and inactivation of human factor VIII by thrombin: Effect of inhibitors of thrombin. Activation and inactivation of human factor VIII Blood 1981; 57: 476-482
    PubMedSearch in Google Scholar
  • 33 Rick ME, Hoyer LW. Thrombin activation of factor VIII: the effect of inhibitors. Br J Haematol 1977; 36: 585-597
    CrossrefPubMedSearch in Google Scholar
  • 34 Fulcher CA, Gardiner JE, Griffin JH, Zimmerman TS. Proteolytic inactivation of human factor VIII procoagulant protein by activated protein C and its analogy with factor V. Blood 1984; 63: 486-489
    PubMedSearch in Google Scholar
  • 35 Pittman DD, Kaufman RJ. Internal deletions of factor VIII identify potentially important peptide sequences for binding to von Willebrand factor. Blood 1987; 70: 392 a
    PubMedSearch in Google Scholar
  • 36 Pittman DD, Wasley LC, Murray BL, Wang JH, Kaufman RJ. Analysis of structural requirements for factor VIII function using site-directed mutagenesis. Thromb Haemostas 1987; 58: 804 a
    PubMedSearch in Google Scholar
  • 37 Huttner WB, Baeuerle PA. Protein sulfation on tyrosine. In: Modern Cell Biology. Birgit SatiriH. (ed) Alan R Liss; Inc NY, NY: 1988. 6 97-140
    Search in Google Scholar
  • 38 Foster PA, Fulcher CA, Houghten RA, Zimmerman TS. An Immunogenic region within residues Val1670-Glu1684 of the factor VIII light chain induces antibodies which inhibit binding of factor VIII to von Willebrand factor. J Biol Chem 1988; 263: 5230-5234
    PubMedSearch in Google Scholar
  • 39 Fay PJ. Reconstitution of human factor VIII from isolated subunits. Arch Biochem Biophys 1988; 262: 525-553
    CrossrefPubMedSearch in Google Scholar
  • 40 Rick MF. Activation of factor VIII by factor IXa. Blood 1982; 60: 744-751
    PubMedSearch in Google Scholar
  • 41 Fay PJ. Thrombin-activated factor VIIIa is composed of a noncovalent 73/51 kD dimer. Thromb Haemostas 1987; 58: 343 (Abstr 1241)
    PubMedSearch in Google Scholar
  • 42 Eaton DL, Hass PE, Riddle L, Mather J, Wiebe M, Gregory T, Vehar GA. Characterization of recombinant human factor VIII. J Biol Chem 1987; 262: 3285-3290
    PubMedSearch in Google Scholar
  • 43 Lollar P, Parker CG. Subunit structure of thrombin-activated porcine factor VIII. Biochemistry 1989; 28: 666-674
    CrossrefPubMedSearch in Google Scholar
  • 44 Nesheim ME, Pittman DD, Wang JH, Slonosky D, Giles AR, Kaufman RJ. The binding of 35S-labeled recombinant factor VIII to activated and unactivated human platelets. J Biol Chem 1988; 263: 16467-16470
    PubMedSearch in Google Scholar
  • 45 Lollar P, Knutson GJ, Fass DN. Stabilization of thrombin-activated porcine factor VIII; C by factor IXa and phospholipid. Blood 1984; 63: 1303-1308
    PubMedSearch in Google Scholar
  • 46 Omar MN, Mann KG. Inactivation of factor Va by plasmin. J Biol Chem 1987; 262: 9750-9755
    PubMedSearch in Google Scholar