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[汉坦病毒G1细胞质尾段功能性类免疫受体酪氨酸激活基序序列的鉴定]

[Identification of a functional ITAM-like sequence within G1 cytoplasmic tail of Hantaan virus].

作者信息

Mou Dan-Lei, Wang Ying-Peng, Jiang Hong, Xiao Shu-Yuan, Yu Xu, Li Guang-Yu, Wang Ping-Zhong, Sun Yong-Tao, Nie Qing-He, Huang Chang-Xing, Bai Xue-Fan

机构信息

Center of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.

出版信息

Bing Du Xue Bao. 2007 Nov;23(6):424-8.

Abstract

The G1 cytoplasmic tail of Hantaan virus (HTNV) harbors a highly conserved region, which is homologous to immunoreceptor tyrosine-based activation motifs (ITAM) and is termed the ITAM-like sequence. To demonstrate the potential signal-transducing activity of G1 ITAM-like sequence resembling the canonical ITAM within immune and endothelial cells, a series of experiments were performed to define its interaction with cellular kinases. The synthesized G1 ITAM-like peptide was shown to coprecipitate with cellular phosphoprotein complexes by an immune-complex kinase assay. Mutational analyses showed that this ITAM-like sequence was a substrate for the Src family kinase Fyn, and two conserved tyrosine residues were required for coprecipitating Lyn, Syk, and ZAP-70 kinases. These findings demonstrated that HTNV envelope glycoprotein G1 contains a functional ITAM-like sequence in its cytoplasmic tail, which can bind critical cellular kinases that regulate immune and endothelial cell functions.

摘要

汉坦病毒(HTNV)的G1胞质尾部含有一个高度保守的区域,该区域与基于免疫受体酪氨酸的激活基序(ITAM)同源,被称为ITAM样序列。为了证明G1 ITAM样序列在免疫细胞和内皮细胞中类似于典型ITAM的潜在信号转导活性,进行了一系列实验来确定其与细胞激酶的相互作用。通过免疫复合物激酶测定法,合成的G1 ITAM样肽显示与细胞磷蛋白复合物共沉淀。突变分析表明,该ITAM样序列是Src家族激酶Fyn的底物,共沉淀Lyn、Syk和ZAP-70激酶需要两个保守的酪氨酸残基。这些发现表明,HTNV包膜糖蛋白G1在其胞质尾部含有一个功能性ITAM样序列,该序列可以结合调节免疫和内皮细胞功能的关键细胞激酶。

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