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克氏锥虫新型GTP酶TcRjl的功能研究揭示了寄生虫分化过程中以及在果蝇模型系统中异源表达后与丝裂原活化蛋白激酶(MAPK)激活相关的表型。

Functional studies of TcRjl, a novel GTPase of Trypanosoma cruzi, reveals phenotypes related with MAPK activation during parasite differentiation and after heterologous expression in Drosophila model system.

作者信息

dos-Santos Guilherme Rodrigo Reis Monteiro, Fontenele Marcio Ribeiro, Dias Felipe de Almeida, de Oliveira Pedro Lagerblad, Nepomuceno-Silva José Luciano, de Melo Luiz Dione Barbosa, Araujo Helena Maria Marcolla, Lopes Ulisses Gazos

机构信息

Laboratório de Parasitologia Molecular, Instituto de Biofísica Carlos Chagas Filho, CCS, UFRJ, Rio de Janeiro, Brazil.

Laboratório de Biologia Molecular do Desenvolvimento Instituto de Ciências Biomédicas, CCS, UFRJ, Rio de Janeiro, Brazil.

出版信息

Biochem Biophys Res Commun. 2015 Nov 6;467(1):115-20. doi: 10.1016/j.bbrc.2015.09.110. Epub 2015 Sep 25.

Abstract

The life cycle of the protozoan parasite Trypanosoma cruzi comprises rounds of proliferative cycles and differentiation in distinct host environments. Ras GTPases are molecular switches that play pivotal regulatory functions in cell fate. Rjl is a novel GTPase with unknown function. Herein we show that TcRjl blocks in vivo cell differentiation. The forced expression of TcRjl leads to changes in the overall tyrosine protein phosphorylation profile of parasites. TcRjl expressing parasites sustained DNA synthesis regardless the external stimuli for differentiation. Heterologous expression in the Drosophila melanogaster genetic system strongly suggests a role from TcRjl protein in RTK-dependent pathways and MAPK activation.

摘要

原生动物寄生虫克氏锥虫的生命周期包括在不同宿主环境中的多轮增殖周期和分化。Ras GTP酶是在细胞命运中发挥关键调节功能的分子开关。Rjl是一种功能未知的新型GTP酶。在此我们表明,TcRjl在体内阻断细胞分化。TcRjl的强制表达导致寄生虫整体酪氨酸蛋白磷酸化谱的变化。表达TcRjl的寄生虫无论外部分化刺激如何都能持续进行DNA合成。在黑腹果蝇遗传系统中的异源表达强烈表明TcRjl蛋白在依赖受体酪氨酸激酶的途径和丝裂原活化蛋白激酶激活中发挥作用。

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