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日本血吸虫丝裂原活化蛋白激酶(MAPK)信号通路的重建与计算机模拟分析

Reconstruction and in silico analysis of the MAPK signaling pathways in the human blood fluke, Schistosoma japonicum.

作者信息

Wang Lili, Yang Zhong, Li Yuanyuan, Yu Fudong, Brindley Paul J, McManus Donald P, Wei Dongzhi, Han Zeguang, Feng Zheng, Li Yixue, Hu Wei

机构信息

State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, 130 Mei-long Road, Shanghai 200237, PR China.

出版信息

FEBS Lett. 2006 Jun 26;580(15):3677-86. doi: 10.1016/j.febslet.2006.05.055.

DOI:10.1016/j.febslet.2006.05.055
PMID:16765950
Abstract

At present, little is known about signal transduction mechanisms in schistosomes, which cause the disease of schistosomiasis. The mitogen-activated protein kinase (MAPK) signaling pathways, which are evolutionarily conserved from yeast to Homo sapiens, play key roles in multiple cellular processes. Here, we reconstructed the hypothetical MAPK signaling pathways in Schistosoma japonicum and compared the schistosome pathways with those of model eukaryote species. We identified 60 homologous components in the S. japonciumMAPK signaling pathways. Among these, 27 were predicted to be full-length sequences. Phylogenetic analysis of these proteins confirmed the evolutionary conservation of the MAPK signaling pathways. Remarkably, we identified S. japonicum homologues of GTP-binding protein beta and alpha-I subunits in the yeast mating pathway, which might be involved in the regulation of different life stages and female sexual maturation processes as well in schistosomes. In addition, several pathway member genes, including ERK, JNK, Sja-DSP, MRAS and RAS, were determined through quantitative PCR analysis to be expressed in a stage-specific manner, with ERK, JNK and their inhibitor Sja-DSP markedly upregulated in adult female schistosomes.

摘要

目前,对于引起血吸虫病的血吸虫的信号转导机制了解甚少。丝裂原活化蛋白激酶(MAPK)信号通路在进化上从酵母到智人都是保守的,在多种细胞过程中发挥关键作用。在此,我们重建了日本血吸虫中假定的MAPK信号通路,并将血吸虫的通路与模式真核生物物种的通路进行了比较。我们在日本血吸虫MAPK信号通路中鉴定出60个同源成分。其中,27个被预测为全长序列。对这些蛋白质的系统发育分析证实了MAPK信号通路的进化保守性。值得注意的是,我们在酵母交配途径中鉴定出了日本血吸虫GTP结合蛋白β和α-I亚基的同源物,它们可能参与血吸虫不同生命阶段的调控以及雌性性成熟过程。此外,通过定量PCR分析确定,包括ERK、JNK、Sja-DSP、MRAS和RAS在内的几个通路成员基因以阶段特异性方式表达,ERK、JNK及其抑制剂Sja-DSP在成年雌性血吸虫中显著上调。

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