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Kidney Plasminogen Activator: A Precursor Form of Human Urokinase With High Fibrin Affinity

Abstract

A systematic screen of human kidney tissue samples has resulted in the establishment of a permanent cell line, TCL-598, which produces and secretes into the medium milligrams per liter quantities of a urokinase-like plasminogen activator. Analysis of the properties of this enzyme indicate that it is a single polypeptide chain of approximately 50,000 molecular weight, it exhibits strong affinity for fibrin, and it is inactive. In the presence of plasmin, however, it is converted into an active two chain enzyme indistinguishable from the familiar high molecular weight form of urokinase. We have termed this pro-urokinase derived from TCL-598 kidney plasminogen activator (KPA). The establishment of fibrin/Celite affinity for this inactive precursor suggests a unique potential for KPA in the treatment of acute vascular diseases such as myocardial infarct, stroke, or deep vein thrombosis.

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Kohno, T., Hopper, P., Lillquist, J. et al. Kidney Plasminogen Activator: A Precursor Form of Human Urokinase With High Fibrin Affinity. Nat Biotechnol 2, 628–634 (1984). https://doi.org/10.1038/nbt0784-628

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