Deletion or replacement of the second EGF-hke domain of protein S results in loss of APC cofactor activity

被引：24

作者：

Mille-Baker, B ^{[1
]}

Rezende, SM ^{[1
]}

Simmonds, RE ^{[1
]}

Mason, PJ ^{[1
]}

Lane, DA ^{[1
]}

Laffan, MA ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Dept Haematol, London W12 0NN, England

来源：

BLOOD | 2003年 / 101卷 / 04期

关键词：

D O I：

10.1182/blood-2002-08-2353

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Human protein S (PS), a cofactor of anticoagulant-activated protein C (AIRC), is a modular protein containing 4 epidermal growth factor (EGF)-like domains. EGF1 appears to mediate PS interaction with APC, but the roles of EGFs 2, 3, and 4 are less clear. We synthesized PS variants lacking single EGF domains (EGF2, 3, or 4) and assessed their APC cofactor activity in a factor Va inactivation assay. The variant lacking EGF2 (variant 134) showed the most dramatic loss of activity (similar to10% of recombinant wild-type PS activity). Replacement of EGF2 by an additional EGF3 (variant 1334) resulted in a comparable loss of activity, suggesting that the loss of a specific rather than "spacer" function of EGF2 was responsible. We con-firmed that the variant 134 had a functional,gamma-carboxyglutamic acid (Gla) domain and that EGF1 was correctly folded. This is the first clear evidence that EGF2 is required for the expression of PS activity. (C) 2003 by The American Society of Hematology.

引用

页码：1416 / 1418

页数：3

共 25 条

[1] Implication of protein S thrombin-sensitive region with membrane binding via conformational changes in the γ-carboxyglutamic acid-rich domain [J].