scholarly journals Effects of Prothrombin on the Individual Activated Protein C-mediated Cleavages of Coagulation Factor Va

2008 ◽  
Vol 283 (11) ◽  
pp. 6648-6655 ◽  
Author(s):  
Sinh Tran ◽  
Eva Norstrøm ◽  
Björn Dahlbäck
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Coagulation Factor ◽  
Factor Va ◽  
The Individual

scholarly journals Effects of Factor Xa and Protein S on the Individual Activated Protein C-mediated Cleavages of Coagulation Factor Va

2006 ◽  
Vol 281 (42) ◽  
pp. 31486-31494 ◽  
Author(s):  
Eva A. Norstrøm ◽  
Sinh Tran ◽  
Mårten Steen ◽  
Björn Dahlbäck
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Protein S ◽  
Factor Va ◽  
The Individual

scholarly journals Effects of Factor Xa and Protein S on the Individual Activated Protein C-mediated Cleavages of Coagulation Factor Va

2006 ◽  
Vol 281 (42) ◽  
pp. 31486-31494
Author(s):  
Eva A. Norstrøm ◽  
Sinh Tran ◽  
Mårten Steen ◽  
Bjo¨rn Dahlba¨ck
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Protein S ◽  
Factor Va ◽  
The Individual

scholarly journals Enhanced Rate of Cleavage at Arg-306 and Arg-506 in Coagulation Factor Va by Gla Domain-mutated Human-activated Protein C

2004 ◽  
Vol 279 (46) ◽  
pp. 47528-47535 ◽  
Author(s):  
Yong-Hui Sun ◽  
Sinh Tran ◽  
Eva A. Norstrøm ◽  
Björn Dahlbäck
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Coagulation Factor ◽  
Factor Va ◽  
Gla Domain

C4b-Binding Protein Protects Coagulation Factor Va from Inactivation by Activated Protein C†

Biochemistry ◽  
2000 ◽  
Vol 39 (47) ◽  
pp. 14543-14548 ◽  
Author(s):  
Robbert H. L. van de Poel ◽  
Joost C. M. Meijers ◽  
Jan Rosing ◽  
Guido Tans ◽  
Bonno N. Bouma
Keyword(s):  
Protein C ◽  
Binding Protein ◽  
Activated Protein C ◽  
Coagulation Factor ◽  
Factor Va

scholarly journals Interdomain engineered disulfide bond permitting elucidation of mechanisms of inactivation of coagulation factor Va by activated protein C

2009 ◽  
Vol 11 (9) ◽  
pp. 2091-2101 ◽  
Author(s):  
Andrew J. Gale ◽  
Xiao Xu ◽  
Jean-Luc Pellequer ◽  
Elizabeth D. Getzoff ◽  
John H. Griffin
Keyword(s):  
Disulfide Bond ◽  
Protein C ◽  
Activated Protein C ◽  
Coagulation Factor ◽  
Factor Va

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

2009 ◽  
Vol 101 (01) ◽  
pp. 55-61 ◽  
Author(s):  
Subramanian Yegneswaran ◽  
Phuong Nguyen ◽  
John Griffin ◽  
Andrew Gale
Keyword(s):  
Protein Interactions ◽  
Protein C ◽  
Activated Protein C ◽  
Coagulation Factor ◽  
Critical Micellar Concentration ◽  
General Concept ◽  
Phospholipid Vesicle ◽  
Amino Terminal ◽  
Factor Va ◽  
Gla Domain

SummaryThe 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 Arg506 and Arg306 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-PheProArg-CMK-inhibited meizothrombin and fII-fragment 1•2 protected FVa from proteolysis by APC. In contrast, no significant protection of FVa from APC cleavage was observed for Gladomainless-FII, prethrombin-1, prethrombin-2, FII fragment 1 or active site inhibited-thrombin (DEGR-thrombin). Overall, these data demonstrate that the Gla domain of FII linked to kringle 1 and 2 is necessary for the ability of FII to protect FVa from APC cleavage and support the general concept that assembly of the FII activation complex (FXa•FVa•FII•lipid surface) protects FVa from APC inactivation so that the procoagulant, thrombin generating pathway can act unhindered by APC. Only following FII activation and dissociation of the FII Gla domain fragments from the FII-ase complex, can APC inactivate FVa and down-regulate thrombin generation.

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