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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1071

Osterwalder, T; Cinelli, P; Baici, A; Pennella, A; Krueger, S R; Schrimpf, S P; Meins, M; Sonderegger, P (1998). The axonally secreted serine proteinase inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin. Journal of Biological Chemistry, 273(4):2312-2321.


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Neuroserpin is an axonally secreted serine proteinase inhibitor that is expressed in neurons during embryogenesis and in the adult nervous system. To identify target proteinases, we used a eucaryotic expression system based on the mouse myeloma cell line J558L and vectors including a promoter from an Ig-kappa-variable region, an Ig-kappa enhancer, and the exon encoding the Ig-kappa constant region (C kappa) and produced recombinant neuroserpin as a wild-type protein or as a fusion protein with C kappa. We investigated the capability of recombinant neuroserpin to form SDS-stable complexes with, and to reduce the amidolytic activity of, a variety of serine proteinases in vitro. Consistent with its primary structure at the reactive site, neuroserpin exhibited inhibitory activity against trypsin-like proteinases. Although neuroserpin bound and inactivated plasminogen activators and plasmin, no interaction was observed with thrombin. A reactive site mutant of neuroserpin neither formed complexes with nor inhibited the amidolytic activity of any of the tested proteinases. Kinetic analysis of the inhibitory activity revealed neuroserpin to be a slow binding inhibitor of plasminogen activators and plasmin. Thus, we postulate that neuroserpin could represent a regulatory element of extracellular proteolytic events in the nervous system mediated by plasminogen activators or plasmin.




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Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
DDC:570 Life sciences; biology
Date:23 January 1998
Deposited On:11 Feb 2008 12:20
Last Modified:27 Nov 2013 23:55
Publisher:American Society for Biochemistry and Molecular Biology
Funders:Olga Mayenfisch Stiftung, Helmut Horten Stiftung, Ciba-Geigy-Jubiläumsstiftung, Hartmann Müller-Stiftung, EMDO-Stiftung, Wolfermann-Nägeli-Stiftung, Union Bank of Switzerland on behalf of a client.
Publisher DOI:10.1074/jbc.273.4.2312
Related URLs:http://www.jbc.org/cgi/content/full/273/4/2312
PubMed ID:9442076

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