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五种人类致病锥虫的TryPIKinome:布氏锥虫、克氏锥虫、硕大利什曼原虫、巴西利什曼原虫和婴儿利什曼原虫——设计特异性抑制剂的新工具

The TryPIKinome of five human pathogenic trypanosomatids: Trypanosoma brucei, Trypanosoma cruzi, Leishmania major, Leishmania braziliensis and Leishmania infantum--new tools for designing specific inhibitors.

作者信息

Bahia Diana, Oliveira Luciana Márcia, Lima Fabio Mitsuo, Oliveira Priscila, Silveira José Franco da, Mortara Renato Arruda, Ruiz Jerônimo Conceição

机构信息

Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil.

出版信息

Biochem Biophys Res Commun. 2009 Dec 18;390(3):963-70. doi: 10.1016/j.bbrc.2009.10.086. Epub 2009 Oct 21.

Abstract

Phosphatidylinositol (PI) kinases are at the heart of one of the major pathways of intracellular signal transduction. Herein, we present the first report on a survey made by similarity searches against the five human pathogenic trypanosomatids Trypanosoma brucei, Trypanosoma cruzi, Leishmania major, Leishmania braziliensis and Leishmania infantum genomes available to date for phosphatidylinositol- and related-kinases (TryPIKs). In addition to generating a panel called "The TryPIKinome", we propose a model of signaling pathways for these TryPIKs. The involvement of TryPIKs in fundamental pathways, such as intracellular signal transduction and host invasion processes, makes the study of TryPIKs an important area for further inquiry. New subtype-specific inhibitors are expected to work on individual members of the PIK family and, therefore, can presumably neutralize trypanosomatid invasion processes.

摘要

磷脂酰肌醇(PI)激酶处于细胞内信号转导主要途径之一的核心位置。在此,我们首次报告了通过相似性搜索,对目前可获取的五种人类致病锥虫(布氏锥虫、克氏锥虫、硕大利什曼原虫、巴西利什曼原虫和婴儿利什曼原虫)基因组中的磷脂酰肌醇及相关激酶(TryPIKs)进行的一项调查。除了生成一个名为“The TryPIKinome”的数据集外,我们还为这些TryPIKs提出了信号通路模型。TryPIKs参与细胞内信号转导和宿主入侵过程等基本途径,这使得对TryPIKs的研究成为一个重要的待进一步探究领域。预计新的亚型特异性抑制剂将作用于PIK家族的各个成员,因此可能中和锥虫的入侵过程。

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