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曼氏血吸虫酪氨酸激酶的功能多样性

Functional Diversity of the Schistosoma mansoni Tyrosine Kinases.

作者信息

Avelar Lívia G A, Nahum Laila A, Andrade Luiza F, Oliveira Guilherme

机构信息

Grupo de Genômica e Biologia Computacional, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, 30190-002 Belo Horizonte, MG, Brazil.

出版信息

J Signal Transduct. 2011;2011:603290. doi: 10.1155/2011/603290. Epub 2011 Jun 15.

Abstract

Schistosoma mansoni, one of the causative agents of schistosomiasis, has a complex life cycle infecting over 200 million people worldwide. Such a successful and prolific parasite life cycle has been shown to be dependent on the adaptive interaction between the parasite and hosts. Tyrosine kinases (TKs) play a key role in signaling pathways as demonstrated by a large body of experimental work in eukaryotes. Furthermore, comparative genomics have allowed the identification of TK homologs and provided insights into the functional role of TKs in several biological systems. Finally, TK structural biology has provided a rational basis for obtaining selective inhibitors directed to the treatment of human diseases. This paper covers the important aspects of the phospho-tyrosine signaling network in S. mansoni, Caenorhabditis elegans, and humans, the main process of functional diversification of TKs, that is, protein-domain shuffling, and also discusses TKs as targets for the development of new anti-schistosome drugs.

摘要

曼氏血吸虫是血吸虫病的病原体之一,其复杂的生命周期感染了全球超过2亿人。如此成功且多产的寄生虫生命周期已被证明依赖于寄生虫与宿主之间的适应性相互作用。酪氨酸激酶(TKs)在信号通路中起关键作用,大量真核生物实验工作已证明了这一点。此外,比较基因组学已使TK同源物得以鉴定,并为TKs在多个生物系统中的功能作用提供了见解。最后,TK结构生物学为获得针对人类疾病治疗的选择性抑制剂提供了合理依据。本文涵盖了曼氏血吸虫、秀丽隐杆线虫和人类中磷酸酪氨酸信号网络的重要方面,TKs功能多样化的主要过程,即蛋白质结构域重排,还讨论了将TKs作为开发新型抗血吸虫药物的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f23b/3135232/e6c8079d29c8/JST2011-603290.001.jpg

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