Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1

Ann Gils, Katrine Egelund Pedersen, Peter Skottrup, Anni Christensen, Dominik Naessens, Johanna Deinum, Jan Johannes Enghild, Paul Declerck, Peter Andreasen

    Research output: Contribution to journalJournal articleResearchpeer-review


    The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous glycosylation pattern of the sites at N209 and N265, while that at N329 is not utilised. The IC(50)-values for inactivation of PAI-1 by 4 monoclonal antibodies differed strongly between glycosylated PAI-1 and non-glycosylated PAI-1 expressed in E. coli. For 3 antibodies, an overlap of the epitopes with the glycosylation sites could be excluded as explanation for the differential reactivity. The latency transition of non-glycosylated, but not of glycosylated PAI-1, was strongly accelerated by a non-ionic detergent. The different biochemical properties of glycosylated and non-glycosylated PAI-1 depended specifically on glycosylation of either one or the other of the utilised sites. The PAI-1-binding protein vitronectin reversed the changes associated with the lack of glycosylation at one of the sites. Our results stress the importance of the source of PAI-1 when studying the mechanisms of action of PAI-1-inactivating compounds of potential clinical importance.
    Original languageEnglish
    JournalThrombosis and Haemostasis
    Issue number2
    Pages (from-to)206-217
    Publication statusPublished - 2003


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