PMID: 2505252Sep 1, 1989Paper

Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

Proceedings of the National Academy of Sciences of the United States of America
D C Hill-EubanksP Lollar

Abstract

Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. We isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO4/PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated fVIII to function as a cofactor in the activation of factor X by factor IXa, we found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated...Continue Reading

References

Jan 24, 1989·Biochemistry·P Lollar, C G Parker
Jan 1, 1988·Annual Review of Biochemistry·K G MannS Krishnaswamy
Jun 23, 1986·Biochimica Et Biophysica Acta·P J FayV J Marder
Jul 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·R J JennyK G Mann
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D D Pittman, R J Kaufman
Dec 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·K M BrinkhousM S Read
Dec 31, 1985·Biochemistry·P LollarD N Fass
Nov 22, 1984·Nature·G A VeharD J Capon

❮ Previous
Next ❯

Citations

Jun 1, 1993·Toxicon : Official Journal of the International Society on Toxinology·M L Santoro, I S Sano-Martins
Dec 1, 1990·Current Opinion in Biotechnology·R J Kaufman
Oct 16, 2003·Toxicon : Official Journal of the International Society on Toxinology·Luiz A BenvenutiJoão L C Cardoso
Jan 24, 2002·Biomaterials·Yasushi TamadaKohei Goto
Dec 20, 2003·Blood Reviews·Philip J Fay
Jan 5, 1999·Haemophilia : the Official Journal of the World Federation of Hemophilia·R J Kaufman, S W Pipe
Jan 6, 1994·The New England Journal of Medicine·L W Hoyer
Jun 19, 2012·The Journal of Biological Chemistry·Mettine H A Bos, Rodney M Camire
Sep 25, 1999·Human Gene Therapy·R J Kaufman
Jun 1, 1993·British Journal of Haematology·G Kemball-CookT W Barrowcliffe
May 1, 1991·Mayo Clinic Proceedings·P Lollar
Jan 12, 2011·Journal of Biotechnology·Mille Petersen KolindLaust Bruun Johnsen
Nov 6, 2008·Journal of Thrombosis and Haemostasis : JTH·S ButenasK G Mann
Sep 22, 2009·Journal of Thrombosis and Haemostasis : JTH·R M Camire, M H A Bos
Oct 22, 2013·Toxicon : Official Journal of the International Society on Toxinology·Liliane Maria Fernandes de OliveiraRaghuvir K Arni
Jan 26, 2013·Blood·Rebecca C MarkovitzPete Lollar
Nov 26, 2015·Scientific Reports·Michelle E WuerthP Clint Spiegel
Mar 4, 2006·The Journal of Biological Chemistry·Ernest T ParkerPete Lollar
Jan 1, 1991·Annals of the New York Academy of Sciences·D N Fass
Aug 28, 2019·Journal of Thrombosis and Haemostasis : JTH·Ian W SmithPaul Clint Spiegel
Apr 14, 1995·The Journal of Biological Chemistry·L M Regan, P J Fay
Apr 25, 2000·The Journal of Biological Chemistry·S S AhmadP N Walsh
Jun 7, 1996·The Journal of Biological Chemistry·C T Esmon, P Lollar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.