The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation
The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation
复制标题
DOI：
10.1038/sj.emboj.7601598
复制
发表时间：
2007-03-21
期刊：
影响因子：
11.4
通讯作者：
Wei, Li-Na
中科院分区：
文献类型：
--
作者：
Tsai, Nien-Pei;Bi, Jing;Wei, Li-Na
我们先前报道了Netrin-1在κ阿片受体（KOR）翻译刺激中的新生物活性。我们现在确定Grb 7作为一种新的RNA结合蛋白，作为分子适配器传递Netrin-1信号，通过黏着斑激酶（FAK），翻译机器。Grb 7通过位于其氨基末端的新的RNA结合结构域特异性结合kor mRNA 5 '-UTR的第一茎环。在结合到其加帽的靶mRNA后，Grb 7阻断eIF 4 E的募集，使mRNA不可翻译。FAK介导的羧基端两个酪氨酸残基的过度磷酸化降低了RNA结合和抑制活性。本研究报道了一种衔接蛋白Grb 7，其将Netrin-1的刺激信号传递到翻译机器以快速调节mRNA翻译。
We previously reported a novel biological activity of Netrin-1 in translational stimulation of kappa opioid receptor (KOR). We now identify Grb7 as a new RNA-binding protein that serves as the molecular adaptor for transmitting Netrin-1 signals, through focal adhesion kinase (FAK), to the translation machinery. Grb7 binds specifically to the first stem loop of kor mRNA 5'-UTR through a new RNA-binding domain located in its amino terminus. Upon binding to its capped, target mRNA, Grb7 blocks the recruitment of eIF4E,rendering mRNA untranslatable. The RNA-binding and translation-repressive activity is reduced by FAK-mediated hyperphosphorylation on two tyrosine residues of its carboxyl terminus. This study reports an adaptor protein Grb7 that transmits the stimulating signals of Netrin-1 to the translational machinery to rapidly regulate mRNA translation.