The CAP1/Prss8 catalytic triad is not involved in PAR2 activation and protease nexin-1 (PN-1) inhibition.

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Serval ID
serval:BIB_7DA29C9C67E9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The CAP1/Prss8 catalytic triad is not involved in PAR2 activation and protease nexin-1 (PN-1) inhibition.
Journal
Faseb Journal
Author(s)
Crisante G., Battista L., Iwaszkiewicz J., Nesca V., Mérillat A.M., Sergi C., Zoete V., Frateschi S., Hummler E.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Publication state
Published
Issued date
11/2014
Peer-reviewed
Oui
Volume
28
Pages
1-14
Language
english
Notes
Publication types: JOURNAL ARTICLE
Abstract
Serine proteases, serine protease inhibitors, and protease-activated receptors (PARs) are responsible for several human skin disorders characterized by impaired epidermal permeability barrier function, desquamation, and inflammation. In this study, we addressed the consequences of a catalytically dead serine protease on epidermal homeostasis, the activation of PAR2 and the inhibition by the serine protease inhibitor nexin-1. The catalytically inactive serine protease CAP1/Prss8, when ectopically expressed in the mouse, retained the ability to induce skin disorders as well as its catalytically active counterpart (75%, n=81). Moreover, this phenotype was completely normalized in a PAR2-null background, indicating that the effects mediated by the catalytically inactive CAP1/Prss8 depend on PAR2 (95%, n=131). Finally, nexin-1 displayed analogous inhibitory capacity on both wild-type and inactive mutant CAP1/Prss8 in vitro and in vivo (64% n=151 vs. 89% n=109, respectively), indicating that the catalytic site of CAP1/Prss8 is dispensable for nexin-1 inhibition. Our results demonstrate a novel inhibitory interaction between CAP1/Prss8 and nexin-1, opening the search for specific CAP1/Prss8 antagonists that are independent of its catalytic activity.-Crisante, G., Battista, L., Iwaszkiewicz, J., Nesca, V., Mérillat, A.-M., Sergi, C., Zoete, V., Frateschi, S., Hummler, E. The CAP1/Prss8 catalytic triad is not involved in PAR2 activation and protease nexin-1 (PN-1) inhibition.
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05/09/2014 16:18
Last modification date
17/09/2020 8:22
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