Molecular Cloning and Characterization of a P38-Like Mitogen-Activated Protein Kinase from Echinococcus granulosus.
Molecular Cloning and Characterization of a P38-Like Mitogen-Activated Protein Kinase from Echinococcus granulosus.
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细粒棘球绦虫 P38 样丝裂原激活蛋白激酶的分子克隆和表征
DOI：
10.3347/kjp.2016.54.6.759
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Lin R
中科院分区：
文献类型：
--
作者：
Lü G;Li J;Zhang C;Li L;Bi X;Li C;Fan J;Lu X;Vuitton DA;Wen H;Lin R
囊状棘球蚴病（CE）的治疗迫切需要一种新的药物。p38丝裂原活化蛋白激酶（MAPK）是一个丝氨酸/苏氨酸蛋白激酶家族，但在细粒棘球绦虫中的特性尚不清楚。我们在大肠杆菌中克隆了一个长度为1,107 bp的编码368个氨基酸的MAPK蛋白（Egp 38）的cDNA。颗粒状。Egp 38具有p38样激酶的两个显著特征：高度保守的T-X-Y基序和激活环片段。结构同源性建模表明Egp 38、EmMPK 2和H. sapiens p38α，这意味着一个共同的结合机制的配体结构域和下游信号转导过程类似于p38α所描述的。Egp 38及其磷酸化形式在E.颗粒虫幼虫在中间宿主感染中间宿主期间经历囊泡和原蛹期。用p38-MAPK抑制剂ML 3403处理体外培养的原螯虾有效地抑制了Egp 38活性，并在5天内导致原螯虾显著死亡。用TGF-β1处理体外培养的原核细胞有效地诱导Egp 38磷酸化。总之，MAPK，Egp 38，在E.颗粒体作为抗CE药物的靶点，参与宿主与E.通过人TGF-β1表达。
Cystic echinococcosis (CE) treatment urgently requires a novel drug. The p38 mitogen-activated protein kinases (MAPKs) are a family of Ser/Thr protein kinases, but still have to be characterized in Echinococcus granulosus. We identified a 1,107 bp cDNA encoding a 368 amino acid MAPK protein (Egp38) in E. granulosus. Egp38 exhibits 2 distinguishing features of p38-like kinases: a highly conserved T-X-Y motif and an activation loop segment. Structural homology modeling indicated a conserved structure among Egp38, EmMPK2, and H. sapiens p38α, implying a common binding mechanism for the ligand domain and downstream signal transduction processing similar to that described for p38α. Egp38 and its phosphorylated form are expressed in the E. granulosus larval stages vesicle and protoscolices during intermediate host infection of an intermediate host. Treatment of in vitro cultivated protoscolices with the p38-MAPK inhibitor ML3403 effectively suppressed Egp38 activity and led to significant protoscolices death within 5 days. Treatment of in vitro-cultivated protoscolices with TGF-β1 effectively induced Egp38 phosphorylation. In summary, the MAPK, Egp38, was identified in E. granulosus, as an anti-CE drug target and participates in the interplay between the host and E. granulosus via human TGF-β1.