Construction of a plasminogen activator inhibitor-1 variant without measurable affinity to vitronectin but otherwise normal

被引:25
作者
Jensen, JK [1 ]
Durand, MKV [1 ]
Skeldal, S [1 ]
Dupont, DM [1 ]
Bodker, JS [1 ]
Wind, T [1 ]
Andreasen, PA [1 ]
机构
[1] Aarhus Univ, Dept Mol Biol, Lab Cellular Prot Sci, DK-8000 Aarhus C, Denmark
关键词
plasminogen activator inhibitor-1; plasminogen; serpin; vitronectin; adhesion;
D O I
10.1016/S0014-5793(03)01405-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vitronectin (VN) and plasminogen activator inhibitor-1 (PAI-1) have important functional interactions: VN stabilises the protease inhibitory activity of PAI-1 and PAI-1 inhibits binding of adhesion receptors to VN. Having previously mapped the PAI-1 binding area for VN, we have now constructed a PAI-1 variant, R103A-M112A-Q125A, without measurable affinity to VN, but with full protease inhibitory activity and endocytosis receptor binding. As a tool for evaluating the physiological and pathophysiological functions of the PAI-1-VN interaction, our new variant is far superior to the previously widely used PAI-1 variant Q125K, which we have found possesses an only about 10-fold reduced affinity to VN. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:175 / 179
页数:5
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