Urokinase

Literature References: Serine protease which activates plasminogen to plasmin; present in mammalian blood and urine. Produced as prourokinase, q.v., and converted to active form by plasmin or kallikrein, q.q.v. Description of fibrinolytic activity: J. R. B. Williams, Br. J. Exp. Pathol. 32, 530 (1951). Isolation from human urine and activity: T. Astrup, I. Sterndorff, Proc. Soc. Exp. Biol. Med. 81, 675 (1952); G. W. Sobel et al., Am. J. Physiol. 171, 768 (1952). Species specificity and distribution in mammals: S. R. Mohler et al., Am. J. Physiol. 192, 186 (1958). Isoln from human male urine: H. O. Singher, L. Zuckerman, US 2961382 and US 2989440 (1960, 1961 to Ortho); N. O. Kjeldgaard, J. Ploug, US 2983647 (1961 to Lövens Kemiske Fabrik); J. Doczi, US 3081236 (1963 to Warner-Lambert). Prepn of crystalline form: A. Lesuk et al., Science 147, 880 (1965). Two variants of bioactive urokinase, high molecular weight (HMW-UK, ~50 KDa) and low molecular weight (LMW-UK, ~30 KDa) have been identified: W. F. White et al., Biochemistry 5, 2160 (1966). Both are disulfide-linked dimers consisting of a heavy chain (B) and a light chain (A). HMW-UK is converted to LMW-UK by proteolytic cleavage of the A-chain to form the A1-chain. Series of articles on plasminogen activation, fibrinolysis and clinical efficacy: Proc. Serono Symp., Thrombosis and Urokinase 9, 1-257 (1977). Review: F. Duckert, Handb. Exp. Pharmacol. 46, 209-237 (1978). Structural characterization: M. Nobuhara et al., J. Biochem. 90, 225 (1981). Structure and amino acid sequences: W. A. Günzler et al., Z. Physiol. Chem. 363, 133 (1982); G. J. Steffens et al., ibid. 1043; W. A. Günzler et al., ibid. 1155. Expression of gene coding for human urokinase in E. coli: B. Ratzkin et al., Proc. Natl. Acad. Sci. USA 78, 3313 (1981). Clinical evaluation in pulmonary embolism: P. Petitpretz et al., Circulation 70, 861 (1984). Clinical trial following myocardial infarction: H. Kambara et al., Jpn. Circ. J. 51, 1072 (1987). Clinical applications of urokinase-treated tubing: T. Ohshiro et al., Methods Enzymol. 137, 529 (1988). Literature review of thrombolytic therapy: J. A. Kaufman, M. A. Bettmann, Semin. Intervent. Radiol. 9, 159-165 (1992).