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- W4384400581 abstract "Serine protease cascades regulate important physiological processes during infection, from complement activation and coagulation in mammals to melanization and Toll pathway activation in insects. Key components of these cascades in insects are clip domain serine proteases (CLIPs) including the catalytic, c lip domain s erine p roteases (cSPs) and the non-catalytic, c lip domain s erine p rotease h omologs (cSPHs), both of which are essential for the proper functioning of these cascades. In the context of the melanization immune response of insects, CLIPs cascades converge on the activation cleavage of the zymogen prophenoloxidase to active phenoloxidase that initiates melanin biogenesis on microbial surfaces. While we have previously provided insight into the structural hierarchy of cSPHs in these cascades in the mosquito vector of malaria Anopheles gambiae , the hierarchy of cSPs as well as their functional interactions with cSPHs remain largely unknown. Here, we define partially the structural hierarchy of An. gambiae cSPs of the CLIPB family that are key factors in the melanization response and characterize their relative contributions to the anti-bacterial melanization response and to mosquito susceptibility to bacterial infections. Based on in vivo and in vitro assays that gauge the activation cleavage profiles of candidate CLIPs, we also propose that bidirectional interactions between cSPs and cSPHs regulate signal amplification and propagation in these cascades." @default.
- W4384400581 created "2023-07-16" @default.
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- W4384400581 date "2023-07-15" @default.
- W4384400581 modified "2023-10-14" @default.
- W4384400581 title "Insight into the structural hierarchy of the protease cascade that regulates the mosquito melanization response" @default.
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- W4384400581 doi "https://doi.org/10.1101/2023.07.13.548954" @default.
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