Generation of Gla‐domainless FVIIa by cathepsin G‐mediated cleavage

FEBS Letters

Hedner, Ulla¹  Thim, Lars¹  Jacobsen, Jes Kristian¹  Petersen, Lars Christian¹  Christensen, Mogens¹  Nicolaisen, Else Marie¹ 

[1] Novo Nordisk, Novo Alle. DK-2880 Bagsvaerd, Denmark

关键词: FVIIa;    Cathepsin G;    Gla-domainless;    Isoelectric focusing;    SDS-PAGE;    Amino acid sequence analysis;    Gla;    λ-carboxyglutamic acid;    GD-L;    Gla-domainless light chain;    L;    light chain;    H;    heavy chain;    IEF;    isoelectric focusing;    r;    recombinant;    RP;    reverse phase;    Rt;    retention time;    TFPI;    tissue factor pathway inhibitor;    ATIII;    antithrombin III;   

DOI  :  10.1016/0014-5793(92)80989-T

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Cougulation factor VII contains ten λ-carboxyglutamic acid residues in the N-terminal region (Gla-domain) which are essential for the hemostatic function of FVII. The present study shows that granulocyte cathepsin G degrades the Gla-domain of FVIIa in vitro. Characterization of the truncated FVIIa by SDS-PAGE and N-terminal amino acid sequence analysis revealed that cleavage had occurred between Tyr-44 and Ser-45 and that further cleavage was only obtained on extensive cathepsin G exposure. Cleavage of vitamin K-dependent coagulation factors by cathepsin G may play a role in vivo, and it offers a convenient way of obtaining proteins deprived of their Gla-domain for functional and structural studies.

【 授权许可】

Unknown