Lyn, one of the Src-family tyrosine kinases expressed in phagocytes, plays an important role in β2 integrin-signalling pathways in opsonized zymosan-activated macrophage-like U937 cells

Lyn, one of the Src-family tyrosine kinases expressed in phagocytes, plays an important role in β2 integrin-signalling pathways in opsonized zymosan-activated macrophage-like U937 cells
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DOI:
10.1002/cbf.1393
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发表时间:
2007-05-01
影响因子:
3.6
通讯作者:
Suzuki, Kazuhiro
Suzuki, Kazuhiro
中科院分区:
生物学3区
文献类型:
--
作者:
Adachi, Reiko;Suzuki, Kazuhiro

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我们研究了Hck、林恩和Fgr这三种高表达的Ste家族酪氨酸激酶(SFKs)在调理酵母聚糖(OZ)激活的吞噬细胞信号转导通路中的作用。用靶向这些转录物的siRNA处理巨噬细胞样U937细胞,使每种激酶的蛋白质含量降低到未处理细胞的一半以下。在这些siRNA中,靶向林恩的siRNA在降低两种吞噬细胞功能方面是最有效的,即氧化爆发和吞噬作用。c-Cbl(β 2整联蛋白信号传导途径中的多结构域衔接蛋白)的磷酸化也在很大程度上被针对林恩的siRNA处理抑制。因此,对Hek、林恩和Fgr具有高度特异性的siRNA的结果表明,在这三种SFK中,林恩在OZ刺激的吞噬细胞中β 2整联蛋白下游的信号传导途径中起最重要的作用。版权所有(c)2006约翰威利父子有限公司。
We have investigated the contribution of Hck, Lyn and Fgr, highly expressed Ste family tyrosine kinases (SFKs) in signalling pathways in opsonized zymosan (OZ)-activated phagocytes by using short interfering RNAs (siRNAs). Treatment of macrophage-like U937 cells with the siRNAs targeted to these transcripts decreased the protein content of each kinase to less than half that of untreated cells. Among these siRNAs, siRNA targeted to Lyn was the most effective in diminishing two kinds of phagocyte functions, that is oxidative burst and phagocytosis. Phosphorylation of c-Cbl, a multidomain adaptor protein in the beta 2 integrin-signalling pathway, was also largely inhibited by treatment with siRNA to Lyn. Thus, the results with siRNAs highly specific for Hek, Lyn and Fgr suggested that, among these three SFKs, Lyn plays the most important role in signalling pathways downstream of beta 2 integrins in OZ-stimulated phagocytes. Copyright (c) 2006 John Wiley & Sons, Ltd.