期刊
MOLECULAR SYSTEMS BIOLOGY
卷 7, 期 -, 页码 -出版社
WILEY
DOI: 10.1038/msb.2011.79
关键词
cell growth; InR/TOR pathway; interaction proteome; quantitative mass spectrometry; signaling
资金
- ETH Zurich
- Roche Research Foundation
- Deutsche Forschungsgemeinschaft
- SystemsX.ch (WingX)
- Swiss National Science Foundation
- F Hoffmann-La Roche Ltd (Basel, Switzerland)
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. Molecular Systems Biology 7: 547; published online 8 November 2011; doi:10.1038/msb.2011.79
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