The Legionella Effector Kinase LegK7 Hijacks the Host Hippo Pathway to Promote Infection.
The Legionella Effector Kinase LegK7 Hijacks the Host Hippo Pathway to Promote Infection.
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DOI：
10.1016/j.chom.2018.08.004
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发表时间：
2018-09-12
影响因子：
30.3
通讯作者：
Machner MP
中科院分区：
文献类型：
--
作者：
Lee PC;Machner MP
细胞内病原体嗜肺军团菌编码易位效应蛋白，其修饰宿主细胞过程以支持细菌存活和生长。在这里，我们表明，L。嗜肺菌效应蛋白LegK 7通过分子模拟宿主Hippo激酶（哺乳动物中的MST 1）来劫持保守的Hippo信号传导途径，所述宿主Hippo激酶是途径活化的关键调节剂。与Hippo/MST 1一样，LegK 7磷酸化支架蛋白MOB 1，这触发了导致转录调节因子TAZ和YAP 1降解的信号级联反应。转录组分析显示，LegK 7介导的TAZ和YAP 1靶向改变了哺乳动物巨噬细胞的转录谱，巨噬细胞是L.嗜肺菌感染具体来说，转录因子PPARγ（受TAZ调节）靶向的基因表现出表达改变，持续干扰PPARγ活性使巨噬细胞对L.嗜肺菌胞内生长。因此，一个保守的L.嗜肺菌效应激酶利用Hippo途径促进细菌生长和感染。
The intracellular pathogen Legionella pneumophila encodes translocated effector proteins that modify host cell processes to support bacterial survival and growth. Here, we show that the L. pneumophila effector protein LegK7 hijacks the conserved Hippo signaling pathway by molecularly mimicking host Hippo kinase (MST1 in mammals), which is the key regulator of pathway activation. LegK7, like Hippo/MST1, phosphorylates the scaffolding protein MOB1, which triggers a signaling cascade resulting in the degradation of the transcriptional regulators TAZ and YAP1. Transcriptome analysis revealed that LegK7-mediated targeting of TAZ and YAP1 alters the transcriptional profile of mammalian macrophages – a key cellular target of L. pneumophila infection. Specifically, genes targeted by the transcription factor PPARγ, which is regulated by TAZ, displayed altered expression, and continuous interference with PPARγ activity rendered macrophages less permissive to L. pneumophila intracellular growth. Thus, a conserved L. pneumophila effector kinase exploits the Hippo pathway to promote bacterial growth and infection.
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影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
Guan KL
DOI：
10.1126/science.1229556
发表时间：
2012-12-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
O'Connor TJ;Boyd D;Dorer MS;Isberg RR
通讯作者：
Isberg RR
影响因子：
2.9
作者：
Croasdell A;Duffney PF;Kim N;Lacy SH;Sime PJ;Phipps RP
通讯作者：
Phipps RP
影响因子：
56.9
作者：
Hong, JH;Hwang, ES;Yaffe, MB
通讯作者：
Yaffe, MB
DOI：
10.1073/pnas.0306743102
发表时间：
2005-04-26
影响因子：
11.1
作者：
Jones, JR;Barrick, C;Magnuson, MA
通讯作者：
Magnuson, MA