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首页> 外文期刊>PLOS Neglected Tropical Diseases >Protein Kinase C and Extracellular Signal-Regulated Kinase Regulate Movement, Attachment, Pairing and Egg Release in Schistosoma mansoni
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Protein Kinase C and Extracellular Signal-Regulated Kinase Regulate Movement, Attachment, Pairing and Egg Release in Schistosoma mansoni

机译：蛋白激酶C和细胞外信号调节激酶调节曼氏血吸虫的运动，附着，配对和卵子释放。

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Protein kinases C (PKCs) and extracellular signal-regulated kinases (ERKs) are evolutionary conserved cell signalling enzymes that coordinate cell function. Here we have employed biochemical approaches using ‘smart’ antibodies and functional screening to unravel the importance of these enzymes to Schistosoma mansoni physiology. Various PKC and ERK isotypes were detected, and were differentially phosphorylated (activated) throughout the various S. mansoni life stages, suggesting isotype-specific roles and differences in signalling complexity during parasite development. Functional kinase mapping in adult worms revealed that activated PKC and ERK were particularly associated with the adult male tegument, musculature and oesophagus and occasionally with the oesophageal gland; other structures possessing detectable activated PKC and/or ERK included the Mehlis' gland, ootype, lumen of the vitellaria, seminal receptacle and excretory ducts. Pharmacological modulation of PKC and ERK activity in adult worms using GF109203X, U0126, or PMA, resulted in significant physiological disturbance commensurate with these proteins occupying a central position in signalling pathways associated with schistosome muscular activity, neuromuscular coordination, reproductive function, attachment and pairing. Increased activation of ERK and PKC was also detected in worms following praziquantel treatment, with increased signalling associated with the tegument and excretory system and activated ERK localizing to previously unseen structures, including the cephalic ganglia. These findings support roles for PKC and ERK in S. mansoni homeostasis, and identify these kinase groups as potential targets for chemotherapeutic treatments against human schistosomiasis, a neglected tropical disease of enormous public health significance.
机译：蛋白激酶C（PKC）和细胞外信号调节激酶（ERK）是协调细胞功能的进化保守细胞信号酶。在这里，我们采用了使用“智能”抗体和功能筛选的生化方法来阐明这些酶对曼氏血吸虫生理的重要性。检测到各种PKC和ERK同种型，并在曼氏曼氏酵母的各个生命阶段进行差异磷酸化（激活），提示同种型特异性作用和寄生虫发育过程中信号复杂性的差异。成虫中的功能性激酶图谱显示，活化的PKC和ERK与成年雄性外表，肌肉组织和食道特别相关，偶尔与食道腺相关。具有可检测到的激活的PKC和/或ERK的其他结构包括Mehlis腺，卵型，黄tell腔，精囊和排泄管。使用GF109203X，U0126或PMA进行成虫蠕虫PKC和ERK活性的药理学调节会导致明显的生理紊乱，这些蛋白在与血吸虫肌肉活动，神经肌肉协调，生殖功能，附着和配对相关的信号传导途径中占据中心位置。在吡喹酮治疗后的蠕虫中也检测到ERK和PKC的激活增强，与被膜和排泄系统相关的信号增强，激活的ERK定位于先前未见的结构，包括头神经节。这些发现支持了曼氏葡萄球菌体内稳态中PKC和ERK的作用，并将这些激酶组确定为针对人类血吸虫病的化学疗法的潜在靶标，人类血吸虫病是一种被忽视的具有重大公共卫生意义的热带病。

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