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.
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.
|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.|
|Citations:||Web of Science®. Times Cited: 79|
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