Regulation of activated protein C by factor Xa.
In this study, the ability of factor Xa to protect factor Va from proteolysis by activated protein C (APC) was verified. Interestingly, factor X was found to exert a similar effect with a dose-dependence identical to that of factor Xa. The effects of factor X and Xa were abrogated in the presence of protein S. To further assess the interactions of factor Va with factors Xa, X and APC, direct binding studies were performed. Factor X and Xa bound to factor Va with equal efficacy. Both proteins displaced APC from its factor Va binding site. These interactions were calcium-dependent. Although the binding of factor Xa devoid of its principal calcium binding site (the Gla-domain) to factor Va was identical to that observed using the native protein, its APC inhibitory effects were significantly reduced. These findings suggest that the Gla-domain of factor X (Xa) is pivotal in the protection of factor Va from APC.
Jane
S M
SM
Department of Medicine, Monash Medical School, Victoria, Australia.
Hau
L
L
Salem
H H
HH
D001665:Binding Sites; D001777:Blood Coagulation; D002118:Calcium / Q000378:metabolism; D015943:Factor Va / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D011486:Protein C / Q000378:metabolism*; D017293:Protein S
D006023:Glycoproteins; D011486:Protein C; D017293:Protein S; D015943:Factor Va; D005170:Factor X; D015951:Factor Xa; D002118:Calcium