Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome.
Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome.
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DOI：
10.1038/msb.2011.79
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发表时间：
2011-11-08
影响因子：
9.9
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黑腹果蝇的遗传分析已被广泛用于识别控制细胞生长的基因系统，以响应胰岛素和营养素。这些基因中的许多编码胰岛素受体/雷帕霉素靶点（InR/TOR）途径的组分。然而，这种调节系统的生化背景下仍然是很差的特点在果蝇。在这里，我们提出了第一个定量研究，系统地表征的模块化和激素敏感性的相互作用蛋白质组的基础生长控制的dInR/TOR途径。应用定量亲和纯化和质谱，我们确定了58个网络组件之间的97个高置信度的蛋白质相互作用。总之，22%的检测到的相互作用调节胰岛素影响膜近端以及细胞内信号复合物。系统功能分析将网络组件的子集与dTORC 1和dTORC 2活性的控制联系起来。此外，我们的数据表明存在三种不同的dTOR激酶复合物，包括进化保守的dTTT复合物（果蝇TOR，TELO 2，TTI 1）。随后的果蝇遗传学研究表明，dTTT通过dTORC 1和dTORC 2依赖性机制控制细胞生长。
Genetic analysis in Drosophila melanogaster has been widely used to identify a system of genes that control cell growth in response to insulin and nutrients. Many of these genes encode components of the insulin receptor/target of rapamycin (InR/TOR) pathway. However, the biochemical context of this regulatory system is still poorly characterized in Drosophila. Here, we present the first quantitative study that systematically characterizes the modularity and hormone sensitivity of the interaction proteome underlying growth control by the dInR/TOR pathway. Applying quantitative affinity purification and mass spectrometry, we identified 97 high confidence protein interactions among 58 network components. In all, 22% of the detected interactions were regulated by insulin affecting membrane proximal as well as intracellular signaling complexes. Systematic functional analysis linked a subset of network components to the control of dTORC1 and dTORC2 activity. Furthermore, our data suggest the presence of three distinct dTOR kinase complexes, including the evolutionary conserved dTTT complex (Drosophila TOR, TELO2, TTI1). Subsequent genetic studies in flies suggest a role for dTTT in controlling cell growth via a dTORC1- and dTORC2-dependent mechanism.