The SHBG-like region of protein S is crucial for factor V-dependent APC-cofactor function
The SHBG-like region of protein S is crucial for factor V-dependent APC-cofactor function
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DOI：
10.1016/s0014-5793(98)00877-1
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发表时间：
1998-08-14
期刊：
影响因子：
3.5
通讯作者：
de Frutos, PG
中科院分区：
文献类型：
--
作者：
Nyberg, P;Dahlbäck, B;de Frutos, PG
活化蛋白C（APC）通过降解因子Va（FVa）和因子Vma（FVIIIa）来调节血液凝固。蛋白S是FVa降解中APC的辅因子，而FVIIIa降解通过蛋白S和因子V（FV）的协同APC-辅因子活性而增强。为了阐明S蛋白中SHBG样区在表达抗凝血活性中的重要性，构建了重组S蛋白/Gas 6嵌合体。它包括蛋白S的氨基末端一半和Gas 6的SHBG样区域，Gas 6是一种结构相似的蛋白质，没有已知的抗凝特性。与野生型蛋白S相比，蛋白S/Gas 6嵌合体在血浆中表达40-50%的APC-辅因子活性。在APC对FVa的降解中，蛋白S/Gas 6嵌合体的效率仅略低于野生型蛋白S。相反，蛋白S/Gas 6嵌合体在FVIIIa降解系统中不表达FV依赖性APC辅因子活性。这表明SHBG样区域对于蛋白S的APC辅因子活性的表达是重要的，并且表明蛋白S的SHBG样区域在APC介导的FVIIIa失活期间与FV相互作用。(C)1998年欧洲生物化学学会联合会。
Activated protein C (APC) regulates blood coagulation by degrading factor Va (FVa) and factor Vma (FVIIIa). Protein S is a cofactor to APC in the FVa degradation, whereas FVIIIa degradation is potentiated by the synergistic APC-cofactor activity of protein S and factor V (FV). To elucidate the importance of the sex-hormone-binding globulin (SHBG)-like region in protein S for expression of anticoagulant activity, a recombinant protein S/Gas6 chimera was constructed. It comprised the amino-terminal half of protein S and the SHBG-like region of Gas6, a structurally similar protein having no known anticoagulant properties. The protein S/Gas6 chimera expressed 40-50% APC-cofactor activity in plasma as compared to wild-type protein S, In the degradation of FVa by APC, the protein S/Gas6 chimera was only slightly less efficient than wildtype protein S. In contrast, the protein S/Gas6 chimera expressed no FV-dependent APC-cofactor activity in a FVIIIa-degradation system. This demonstrates the SHBG-like region to be important for expression of APC-cofactor activity of protein S and suggests that the SHBG-like region of protein S interacts with FV during the APC-mediated inactivation of FVIIIa. (C) 1998 Federation of European Biochemical Societies.