The SHBG‐like region of protein S is crucial for factor V‐dependent APC‐cofactor function

FEBS Letters

Dahlbäck, Björn¹  Nyberg, Petra¹  Garcı́a de Frutos, Pablo¹ 

[1] Department of Clinical Chemistry, Wallenberg Laboratory, Lund University, University Hospital, S-20502 Malmö, Sweden

关键词: Protein S;    Factor V;    Chimera;    SHBG-like region;    APC-cofactor function;    Hemostasis;    APC;    activated protein C;    EGF;    epidermal growth factor;    FV;    coagulation factor V;    FVa;    activated factor V;    FVIII;    coagulation factor VIII;    FVIIIa;    activated factor VIII;    FIXa;    activated factor IX;    Gla;    γ-carboxyglutamic acid;    SHBG;    sex-hormone-binding globulin;    TBS;    Tris-buffered saline;    TSR;    thrombin-sensitive region;   

DOI  :  10.1016/S0014-5793(98)00877-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Activated protein C (APC) regulates blood coagulation by degrading factor Va (FVa) and factor VIIIa (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 wild-type 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.

【 授权许可】

Unknown