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Thromb Haemost 1992; 68(05): 539-544
DOI: 10.1055/s-0038-1646314
Original Article
Schattauer GmbH Stuttgart

The Influence of Glycosylation on the Catalytic and Fibrinolytic Properties of Pro-Urokinase

Catherine Lenich
The Vascular Research Laboratory, Institute for the Prevention of Cardiovascular Disease, New England Deaconess Hospital, Harvard Medical School, Boston, MA, USA
,
Ralph Pannell
The Vascular Research Laboratory, Institute for the Prevention of Cardiovascular Disease, New England Deaconess Hospital, Harvard Medical School, Boston, MA, USA
,
Jack Henkin
1   The Abbott Laboratories, Division of Research and Development, Abbott Park, IL, USA
,
Victor Gurewich
The Vascular Research Laboratory, Institute for the Prevention of Cardiovascular Disease, New England Deaconess Hospital, Harvard Medical School, Boston, MA, USA
› Author Affiliations
Further Information

Publication History

Received 10 April 1992

Accepted after revision 10 June 1992

Publication Date:
04 July 2018 (online)

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Summary

We previously found that human pro-UK expressed in Escherichia coli is more active in fibrinolysis than recombinant human pro-UK obtained from mammalian cell culture media. To determine whether this difference is related to the lack of glycosylation of the E. coli product, we compared the activity of E. coli-derived pro-UK [(-)pro-UK] with that of a glycosylated pro-UK [(+)pro-UK] and of a mutant of pro-UK missing the glycosylation site at Asn-302 [(-) (302) pro-UK]. The latter two pro-UKs were obtained by expression of the human gene in a mammalian cell. The nonglycosylated pro-UKs were activated by plasmin more efficiently (≈2-fold) and were more active in clot lysis (1.5-fold) than the (+)pro-UK. Similarly, the nonglycosylated two-chain derivatives (UKs) were more active against plasminogen and were more rapidly inactivated by plasma inhibitors than the (+)UK.

These findings indicate that glycosylation at Asn-302 influences the activity of pro-UK/UK and could be the major factor responsible for the enhanced activity of E. coli-derived pro-UK.

 

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