Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Jun;77(6):2048–2051. doi: 10.1172/JCI112535

An explanation for minor multimer species in endothelial cell-synthesized von Willebrand factor.

D C Lynch, T S Zimmerman, E H Ling, P J Browning
PMCID: PMC370567  PMID: 3486890

Abstract

Initial synthesis of von Willebrand factor (vWf) by cultured human endothelial cells proceeds by formation of a dimer of pro-vWf subunits. These subunits are found only within the cell and have an apparent molecular weight of 240,000-260,000, as measured by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels. Posttranslational modifications, including proteolytic cleavage, glycosylation, and sulfation, result in the appearance of two additional vWf subunits. The major one migrates with the subunit of plasma vWf at an apparent molecular weight of 220,000-225,000 and the other migrates more slowly than pro-vWf at an apparent molecular weight of 260,000-275,000. These subunits oligomerize to form a set of vWf multimers, which are subsequently secreted into the culture medium. We isolated individual vWf oligomer species from the agarose gel bands and show that vWf minor, or satellite, species differ from major species in subunit composition.

Full text

PDF

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Davies B. L., Furlong R. A., Peake I. R. Studies on the relationship between factor VIII related antigen (VIIIRAg) and factor VIII clotting antigen (VIIICAg) by immunoelectrophoresis and autoradiography using 125I anti VIIICAg. Thromb Res. 1981 Apr 1;22(1-2):87–96. doi: 10.1016/0049-3848(81)90311-x. [DOI] [PubMed] [Google Scholar]
  2. Hoyer L. W., Shainoff J. R. Factor VIII-related protein circulates in normal human plasma as high molecular weight multimers. Blood. 1980 Jun;55(6):1056–1059. [PubMed] [Google Scholar]
  3. Hoyer L. W. The factor VIII complex: structure and function. Blood. 1981 Jul;58(1):1–13. [PubMed] [Google Scholar]
  4. Jaffe E. A., Hoyer L. W., Nachman R. L. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest. 1973 Nov;52(11):2757–2764. doi: 10.1172/JCI107471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kinoshita S., Harrison J., Lazerson J., Abildgaard C. F. A new variant of dominant type II von Willebrand's disease with aberrant multimeric pattern of factor VIII-related antigen (type IID). Blood. 1984 Jun;63(6):1369–1371. [PubMed] [Google Scholar]
  6. Legaz M. E., Schmer G., Counts R. B., Davie E. W. Isolation and characterization of human Factor VIII (antihemophilic factor). J Biol Chem. 1973 Jun 10;248(11):3946–3955. [PubMed] [Google Scholar]
  7. Lynch D. C., Williams R., Zimmerman T. S., Kirby E. P., Livingston D. M. Biosynthesis of the subunits of factor VIIIR by bovine aortic endothelial cells. Proc Natl Acad Sci U S A. 1983 May;80(9):2738–2742. doi: 10.1073/pnas.80.9.2738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lynch D. C., Zimmerman T. S., Collins C. J., Brown M., Morin M. J., Ling E. H., Livingston D. M. Molecular cloning of cDNA for human von Willebrand factor: authentication by a new method. Cell. 1985 May;41(1):49–56. doi: 10.1016/0092-8674(85)90060-1. [DOI] [PubMed] [Google Scholar]
  9. Lynch D. C., Zimmerman T. S., Kirby E. P., Livingston D. M. Subunit composition of oligomeric human von Willebrand factor. J Biol Chem. 1983 Nov 10;258(21):12757–12760. [PubMed] [Google Scholar]
  10. Mannucci P. M., Lombardi R., Pareti F. I., Solinas S., Mazzucconi M. G., Mariani G. A variant of von Willebrand's disease characterized by recessive inheritance and missing triplet structure of von Willebrand factor multimers. Blood. 1983 Nov;62(5):1000–1005. [PubMed] [Google Scholar]
  11. Ruggeri Z. M., Nilsson I. M., Lombardi R., Holmberg L., Zimmerman T. S. Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC). J Clin Invest. 1982 Nov;70(5):1124–1127. doi: 10.1172/JCI110700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ruggeri Z. M., Zimmerman T. S. Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest. 1980 Jun;65(6):1318–1325. doi: 10.1172/JCI109795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Wagner D. D., Marder V. J. Biosynthesis of von Willebrand protein by human endothelial cells. Identification of a large precursor polypeptide chain. J Biol Chem. 1983 Feb 25;258(4):2065–2067. [PubMed] [Google Scholar]
  14. Wagner D. D., Marder V. J. Biosynthesis of von Willebrand protein by human endothelial cells: processing steps and their intracellular localization. J Cell Biol. 1984 Dec;99(6):2123–2130. doi: 10.1083/jcb.99.6.2123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Zimmerman T. S., Dent J. A., Ruggeri Z. M., Nannini L. H. Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (types IIC, IID, and IIE). J Clin Invest. 1986 Mar;77(3):947–951. doi: 10.1172/JCI112394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Zimmerman T. S., Ruggeri Z. M., Fulcher C. A. Factor VIII/von Willebrand factor. Prog Hematol. 1983;13:279–309. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES