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Korean J Parasitol. 2016 Dec;54(6):759-768. doi: 10.3347/kjp.2016.54.6.759. Epub 2016 Dec 31.

Molecular Cloning and Characterization of a P38-Like Mitogen-Activated Protein Kinase from Echinococcus granulosus.

Author information

1
Xinjiang Key Laboratory of Echinococcosis, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830054, P. R. China.
2
College of Basic Medicine, Xinjiang Medical University, Urumqi, Xinjiang, China.
3
WHO-Collaborating Centre for the Prevention and Treatment of Human Echinococcosis, Department of Parasitology, University of Franche-Comté (EA 3181) and University Hospital, Besançon, France.

Abstract

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.

KEYWORDS:

Echinococcus granulosus; cystic echinococcosis; p38 MAP kinase; protoscolex

PMID:
28095661
PMCID:
PMC5266364
DOI:
10.3347/kjp.2016.54.6.759
[Indexed for MEDLINE]
Free PMC Article

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