The CAP1/Prss8 Catalytic Triad Is Not Involved in PAR2 Activation and Protease Nexin-1 (PN-1) Inhibition

    August 2014 in “ The FASEB Journal ”
    Giovanna Crisante, Laura Battista, Justyna Iwaszkiewicz, Valeria Nesca, Anne‐Marie Mérillat, Chloé Sergi, Vincent Zoete, Simona Frateschi, Edith Hümmler
    TLDR CAP1/Prss8 does not activate PAR2 or inhibit PN-1.
    The study investigated the role of the catalytically inactive serine protease CAP1/Prss8 in epidermal homeostasis, PAR2 activation, and inhibition by protease nexin-1 (PN-1). It was found that the inactive CAP1/Prss8 could still induce skin disorders in mice, similar to its active form, and this effect was dependent on PAR2. Additionally, nexin-1 inhibited both the wild-type and inactive CAP1/Prss8, indicating that the catalytic site of CAP1/Prss8 was not necessary for nexin-1 inhibition. These findings suggested a novel interaction between CAP1/Prss8 and nexin-1, independent of CAP1/Prss8's catalytic activity, and highlighted the potential for developing specific CAP1/Prss8 antagonists.
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