查看文章

Inactivation of membrane-bound factor Va by activated protein C (APC) proceeds via a biphasic reaction that consists of a rapid and a slow phase, which are associated with cleavages at Arg⁵⁰⁶ and Arg³⁰⁶ of the heavy chain of factor Va, respectively. We have investigated the effects of protein S and factor Xa on APC-catalyzed factor Va inactivation. Protein S accelerates factor Va inactivation by selectively promoting the slow cleavage at Arg³⁰⁶ (20-fold). Factor Xa protects factor Va from inactivation by APC by selectively blocking cleavage at Arg⁵⁰⁶. Inactivation of factor Va^R506Q, which was isolated from the plasma of a homozygous APC-resistant patient and which lacks the Arg⁵⁰⁶ cleavage site, was also stimulated by protein S but was not affected by factor Xa. This confirms that the target sites of protein S and factor Xa involve Arg³⁰⁶ and Arg⁵⁰⁶, respectively. Factor Xa completely blocked APC-catalyzed …