Abstract
Platelet Factor 4 (PF4) prevents inhibition of blood coagulation proteases by heparin via formation of a putative enzyme-PF4 complex. To investigate the contribution of the latter, the activity of factor Xa (fXa) was determined in chromogenic assays measuring hydrolysis of a peptide substrate S2765 or cleavage of the macromolecular substrate prothrombin in the activating complex, prothrombinase. Upon preincubation with fXa and heparin, PF4 at about 250 nM decreased the k(cat) of S2765 hydrolysis about fivefold and that of prothrombin activation about 25-fold. In the presence of saturating fVa, inhibition of fXa by PF4 was abolished, while in the presence of limiting fVa, PF4 altered the interaction of fXa with fVa. Interestingly, high concentrations of PF4 restored fXa activity toward S2765 and prothrombin, indicating a dual effect of PF4 on fXa activities. These findings suggest that PF4 in the presence of heparin is an allosteric effector of the prothrombinase complex.
References
Feb 1, 1980·The Journal of Clinical Investigation·M A Shuman, S P Levine
Feb 1, 1983·The Biochemical Journal·J DentonU Lindahl
Apr 15, 1995·Circulation·G J DehmerE M Bonnem
Jun 1, 1993·Glycobiology·M Maccarana, U Lindahl
Oct 7, 1997·Biochemistry·S Krishnaswamy, A Betz
Jun 27, 1998·The Journal of Biological Chemistry·A R Rezaie
Feb 1, 2000·The Journal of Biological Chemistry·A R Rezaie
Mar 30, 2001·The Journal of Biological Chemistry·N Brufatto, M E Nesheim
Apr 6, 2001·Blood·A R Rezaie
Jan 10, 2002·The Journal of Biological Chemistry·Matthias Wilkens, Sriram Krishnaswamy
Oct 25, 2003·Biochemical and Biophysical Research Communications·Martine M Fiore, Vijay V Kakkar
Jul 30, 2004·Seminars in Thrombosis and Hemostasis·Timothy A Mixon, Gregory J Dehmer
Aug 12, 2004·Blood·Lubica RauovaBruce S Sachais
Nov 16, 2004·Thrombosis and Haemostasis·Steven T OlsonIngemar Björk
May 18, 2005·The Journal of Biological Chemistry·Michael A BukysMichael Kalafatis
Aug 30, 2007·The Journal of Biological Chemistry·Stéphanie LevigneOlivier D Christophe
Citations
Oct 22, 2010·Journal of Thrombosis and Haemostasis : JTH·A SarabiP Von Hundelshausen
Dec 4, 2014·Cytokine & Growth Factor Reviews·Jing LiWan-yee Lau
Mar 29, 2013·The Journal of Biological Chemistry·Je-Hung KuoShih-Che Sue
Jul 6, 2020·Journal of Cardiothoracic and Vascular Anesthesia·Florian FalterMartin Besser