Regulation of Hippo signaling by EGFR-MAPK signaling through Ajuba family proteins.
Regulation of Hippo signaling by EGFR-MAPK signaling through Ajuba family proteins.
复制标题
EGFR-MAPK信号通过Ajuba家族蛋白来调节河马信号传导。
DOI：
10.1016/j.devcel.2013.01.020
复制
发表时间：
2013-03-11
影响因子：
11.8
通讯作者：
Irvine, Kenneth D.
中科院分区：
文献类型：
--
作者：
Reddy, B. V. V. G.;Irvine, Kenneth D.
EGFR和Hippo信号传导都控制生长，并且当失调时有助于肿瘤发生。我们发现，EGFR激活海马通路转录因子Yorkie，并证明Yorkie是必需的EGFR对细胞增殖的影响在果蝇。EGFR通过其Ras-MAPK分支对Ajuba LIM蛋白Jub的影响来调节Yorkie。Jub对于Yorkie调节是对EGFR和Ras上位的，Jub受到MAPK依赖性磷酸化，并且EGFR-Ras-MAPK信号传导增强Jub与Yorkie激酶Warts和衔接蛋白萨尔瓦多的结合。EGFR-Hippo途径联系在哺乳动物中是保守的，因为EGFR或RAS的激活会激活Yorkie同源物雅普，而EGFR-RAS-MAPK信号传导促进Ajuba家族蛋白WTIP的磷酸化，并且还增强WTIP与疣和萨尔瓦多同源物LATS和WW 45的结合。我们的观察牵连海马途径EGFR介导的肿瘤发生，并确定这些途径之间的分子联系。
EGFR and Hippo signaling both control growth, and when dysregulated contribute to tumorigenesis. We find that EGFR activates the Hippo pathway transcription factor Yorkie, and demonstrate that Yorkie is required for the influence of EGFR on cell proliferation in Drosophila. EGFR regulates Yorkie through an influence of its Ras-MAPK branch on the Ajuba LIM protein Jub. Jub is epistatic to EGFR and Ras for Yorkie regulation, Jub is subject to MAPK-dependent phosphorylation, and EGFR-Ras-MAPK signaling enhances Jub binding to the Yorkie kinase Warts, and the adaptor protein Salvador. An EGFR-Hippo pathway link is conserved in mammals, as activation of EGFR or RAS activates the Yorkie homologue YAP, and EGFR-RAS-MAPK signaling promotes phosphorylation of the Ajuba family protein WTIP, and also enhances WTIP binding to the Warts and Salvador homologues LATS and WW45. Our observations implicate the Hippo pathway in EGFR-mediated tumorigenesis and identify a molecular link between these pathways.
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DOI：
10.1016/j.cub.2010.02.035
发表时间：
2010-04-13
期刊：
Current biology : CB
影响因子：
--
作者：
Das Thakur M;Feng Y;Jagannathan R;Seppa MJ;Skeath JB;Longmore GD
通讯作者：
Longmore GD
影响因子：
7.3
作者：
Irvine, Kenneth D.
通讯作者：
Irvine, Kenneth D.
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
5.3
作者：
McFall, A;Ülkü, A;Der, CJ
通讯作者：
Der, CJ
影响因子：
15.8
作者：
Greulich H;Chen TH;Feng W;Jänne PA;Alvarez JV;Zappaterra M;Bulmer SE;Frank DA;Hahn WC;Sellers WR;Meyerson M
通讯作者：
Meyerson M