Prothrombin amino terminal region helps protect coagulation factor Va from proteolytic inactivation by activated protein C.

Thrombosis and Haemostasis
Subramanian YegneswaranJohn H Griffin

Abstract

The hypothesis that prothrombin (FII) protects coagulation factor Va (FVa) from proteolytic inactivation by activated protein C (APC) was tested using purified proteins. FII dose-dependently protected FVa from APC proteolysis under conditions where competition of proteins for binding to negatively-charged phospholipid surface was not relevant (i.e. either at high phospholipid vesicle concentrations or using soluble dicaproylphosphatidylserine at levels below its critical micellar concentration). Cleavages in FVa at both Arg(506) and Arg(306) by APC were inhibited by FII. FII did not alter the amidolytic activity of APC towards chromogenic oligopeptide substrates or inhibit FVIIIa inactivation by APC, implying that the FII-mediated protection of FVa from APC proteolysis was due to the ability of FII to inhibit protein-protein interactions between FVa and APC. FII also protected FVa from inactivation by Gla-domainless APC, ruling out a role for the APC Gla domain for these observations. To identify domains of FII responsible for the observed phenomenon, various forms or fragments of FII were employed. Biotin-Phe-ProArg-CMK-inhibited meizothrombin and fII-fragment 1*2 protected FVa from proteolysis by APC. In contrast, no signific...Continue Reading

Citations

May 21, 2010·The Journal of Biological Chemistry·Gerry A F NicolaesJan Rosing
May 23, 2012·BMC Systems Biology·Maria Cristina BravoStephen J Everse
Dec 17, 2009·Journal of Thrombosis and Haemostasis : JTH·E Castoldi, J Rosing
Oct 8, 2011·Thrombosis and Haemostasis·Jolanta M Siller-MatulaBernd Jilma

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