{"content"=>"Identification of functional MKK3/6 and MEK1/2homologs from and investigation of protoscolecidal activity of MAPK signaling pathway inhibitors and .", "i"=>[{"content"=>"Echinococcus granulosus"}, {"content"=>"in vitro"}, {"content"=>"in vivo"}]} (original) (raw)

2018, Antimicrobial agents and chemotherapy

Cystic echinococcosis is a zoonosis caused by the larval stage of There is an urgent need to develop new drugs for the treatment of this disease. In this study, we identified two new members of MAPK cascades, MKK3/6 and MEK1/2 homologs (termed EgMKK1 and EgMKK2, respectively), from Both EgMKK1 and EgMKK2 were expressed at the larval stages. As shown by yeast two-hybrid and co-immunoprecipitation analyses, EgMKK1 interacted with the previously identified Egp38 but not with EgERK. EgMKK2, on the other hand, interacted with EgERK. In addition, EgMKK1 and EgMKK2 displayed kinase activity toward the substrate, myelin basic protein. When sorafenib tosylate, PD184352 or U0126-EtOH were added to the medium for culture of protoscoleces (PSCs) or cysts, an inhibitory and cytolytic effect was observed via suppressed phosphorylation of EgMKKs and EgERK. Non-viability of PSCs treated with sorafenib tosylate or U0126-EtOH, and not with PD184352, was confirmed through bioassay, i.e. inoculation of...

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