FEBS Letters | |
Characterization of common neoantigenic epitopes generated in plasminogen activator inhibitor‐1 after cleavage of the reactive center loop or after complex formation with various serine proteinases | |
Declerck, Paul J.1  Debrock, Sophie1  | |
[1] Laboratory for Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium | |
关键词: Monoclonal antibody; Plasminogen activator inhibitor; PAI-1; Neoantigenic; Serpin; PAI-1; plasminogen activator inhibitor-1; t-PA; tissue-type plasminogen activator; u-PA; urokinase-type plasminogen activator; ELISA; enzyme linked immunosorbent assay; PBS; phosphate buffered saline; serpin; serine proteinase inhibitor; RAM; rabbit anti-mouse; HRP; horseradish peroxidase; | |
DOI : 10.1016/0014-5793(95)01289-0 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Plasminogen activator inhibitor-1 (PAI-1), an important risk factor for thrombotic diseases, is a member of the superfamily of serine proteinase inhibitors. To define structural rearrangements occurring during interaction between PAI-1 and its target proteinases we have raised monoclonal antibodies against the PAI-1/t-PA complex. Thirteen out of 401 monoclonal antibodies reacted preferentially with the PAI-1/t-PA complex as compared to free PAI-1 or free t-PA. Detailed characterization revealed the presence of two non-overlapping neoantigenic epitopes in the PAI-1/t-PA complex. Both neoantigenic epitopes were also exposed after complex formation between PAI-1 and either urokinase-type plasminogen activator, plasmin or thrombin as well as after cleavage of the reactive site loop of non-inhibitory substrate type PAI-1 variants. Thus, we have identified two neoantigenic epitopes, localized entirely in PAI-1, and commonly exposed after complex formation of active PAI-1 with various proteinases or after cleavage of substrate PAI-1. These monoclonal antibodies should facilitate further studies on the mechanism of interaction between various PAI-1 forms and its target proteinases.
【 授权许可】
Unknown
【 预 览 】
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