Factor V and protein S as synergistic cofactors to activated protein C in degradation of factor VIIIa.

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Factor V and protein S as cofactors to activated protein C.

BACKGROUND AND OBJECTIVE Activated protein C (APC)-resistance, the most common risk factor for venous thrombosis described so far, is due to a single point mutation in the factor V gene. As a result, inactivation of factor-activated factor V by APC is impaired, which leads to a hypercoagulable state and a lifelong increased risk of thrombosis. The importance of protein S as an anticoagulant pro...

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Exosite-dependent regulation of factor VIIIa by activated protein C.

Activated protein C (APC) is a natural anticoagulant serine protease in plasma that down-regulates the coagulation cascade by degrading cofactors Va and VIIIa by limited proteolysis. Recent results have indicated that basic residues of 2 surface loops known as the 39-loop (Lys37-Lys39) and the Ca2+-binding 70-80-loop (Arg74 and Arg75) are critical for the anticoagulant function of APC. Kinetics...

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Regulation of factor VIIIa by human activated protein C and protein S: inactivation of cofactor in the intrinsic factor Xase.

Factor VIIIa is a trimer of A1, A2, and A3-C1-C2 subunits. Inactivation of the cofactor by human activated protein C (APC) results from preferential cleavage at Arg336 within the A1 subunit, followed by cleavage at Arg562 bisecting the A2 subunit. In the presence of human protein S, the rate of APC-dependent factor VIIIa inactivation increased several-fold and correlated with an increased rate ...

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polymorphisms at activated protein c cleavage sites of factor v: are they important in the absence of factor v leiden?

introduction : activated protein c (apc) inactivates factor v by cleavage of its heavy chain at arg306, arg506, arg679, and lys994. mutational changes, which abolish apc cleavage sites, may predispose thrombosis by altering the inactivation process of factor v.  factor v leiden (arg506glu) has been demonstrated as a strong risk factor for thrombosis. in the current study, we have studied whethe...

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Resistance to activated protein C and factor V Leiden.

Over the last four years, there has been an explosion of knowledge about APCr and factor V Leiden. However, there remain a considerable number of difficult clinical areas in which there are no clear answers. Undoubtedly, factor V Leiden is commonly found in association with venous thromboembolic disease in whatever manifestation, but equally it has an unusually high frequency in the general pop...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 1994

ISSN: 0021-9258

DOI: 10.1016/s0021-9258(17)32228-7