Nedd4 controls animal growth by regulating IGF-1 signaling.
Nedd4 controls animal growth by regulating IGF-1 signaling.
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DOI：
10.1126/scisignal.1160940
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发表时间：
2008-09-23
影响因子：
7.3
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Cao XR;Lill NL;Boase N;Shi PP;Croucher DR;Shan H;Qu J;Sweezer EM;Place T;Kirby PA;Daly RJ;Kumar S;Yang B
泛素连接酶Nedd 4已被提出调节许多信号通路，但其在哺乳动物中的生理作用尚未被表征。在这里，我们提出了一个Nedd 4基因缺失小鼠的分析，以表明Nedd 4基因的缺失导致胰岛素样生长因子1（IGF-1）和胰岛素信号转导减少，胚胎发育延迟，生长和体重下降，新生儿死亡。在小鼠胚胎成纤维细胞中，促有丝分裂活性降低，衔接蛋白Grb 10的丰度增加，并且通常存在于质膜上的IGF-1受体被错误定位。然而，在敲低Grb 10后，纯合突变小鼠胚胎成纤维细胞中IGF-1受体的表面表达恢复，并且Nedd 4 −/−致死性被破坏的Grb 10等位基因的母系遗传所挽救。因此，在体内，Nedd 4似乎部分通过调节Grb 10功能来积极控制IGF-1和胰岛素信号传导。
The ubiquitin ligase Nedd4 has been proposed to regulate a number of signaling pathways, but its physiological role in mammals has not been characterized. Here we present an analysis of Nedd4-null mice to show that loss of Nedd4 results in reduced insulin-like growth factor 1 (IGF-1) and insulin signaling, delayed embryonic development, reduced growth and body weight, and neonatal lethality. In mouse embryonic fibroblasts, mitogenic activity was reduced, the abundance of the adaptor protein Grb10 was increased, and the IGF-1 receptor, which is normally present on the plasma membrane, was mislocalized. However, surface expression of IGF-1 receptor was restored in homozygous mutant mouse embryonic fibroblasts after knockdown of Grb10, and Nedd4−/− lethality was rescued by maternal inheritance of a disrupted Grb10 allele. Thus, in vivo, Nedd4 appears to positively control IGF-1 and insulin signaling partly through the regulation of Grb10 function.
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影响因子：
4.8
作者：
Morrione, A;Plant, P;Baserga, R
通讯作者：
Baserga, R
影响因子：
32.4
作者：
Oliver, Paula M.;Cao, Xiao;Yang, Baoli
通讯作者：
Yang, Baoli
影响因子：
4.4
作者：
Kumar, S;Harvey, KF;Jenkins, NA
通讯作者：
Jenkins, NA
影响因子：
4.8
作者：
Dufresne, AM;Smith, RJ
通讯作者：
Smith, RJ
DOI：
10.1073/pnas.1532175100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Charalambous, M;Smith, FM;Ward, A
通讯作者：
Ward, A