Perturbation of epidermal growth factor receptor complex formation and Ras signalling in cells harbouring the hepatitis C virus subgenomic replicon
Perturbation of epidermal growth factor receptor complex formation and Ras signalling in cells harbouring the hepatitis C virus subgenomic replicon
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DOI：
10.1099/vir.0.80724-0
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Harris, M
中科院分区：
文献类型：
--
作者：
Macdonald, A;Chan, JKY;Harris, M
丙型肝炎病毒非结构NS 5A蛋白抑制表皮生长因子（EGF）刺激的Ras-ERK促分裂原活化蛋白激酶途径在Ras活化上游的点的活化。为了确定这种抑制的机制，研究了在携带HCV亚基因组复制子的Huh-7细胞中EGF受体和Ras之间发生的事件。结果表明，EGF刺激后，这些细胞表现出减少EGF受体酪氨酸磷酸化，异常招聘的衔接蛋白ShcA和Grb 2的EGF受体，减少磷酸化的ShcA和减少Ras激活与对照细胞相比。这些数据与NS 5A和/或复制子的其他组分对Ras上游发生的多个事件的影响一致。
Hepatitis C virus non-structural NS5A protein inhibits epidermal growth factor (EGF)-stimulated activation of the Ras-ERK mitogen-activated protein kinase pathway at a point upstream of Ras activation. To determine the mechanism of this inhibition, the events occurring between the EGF receptor and Ras in Huh-7 cells harbouring the HCV subgenomic replicon were investigated. It was shown that, following EGF stimulation, these cells exhibited decreased EGF receptor tyrosine phosphorylation, aberrant recruitment of the adaptor proteins ShcA and Grb2 to the EGF receptor, reduced phosphorylation of ShcA and reduced Ras activation in comparison with control cells. These data are consistent with effects of NS5A and/or other components of the replicon on multiple events occurring upstream of Ras.