Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2013
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| Online Access: | http://hdl.handle.net/1721.1/77992 |
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| author | Jevtov, Irena Glatter, Timo Schittenhelm, Ralf B. Rinner, Oliver Roguska, Katarzyna Wepf, Alexander Junger, Martin A. Kohler, Katja Choi, Hyungwon Schmidt, Alexander Nesvizhskii, Alexey I. Stocker, Hugo Hafen, Ernst Aebersold, Ruedi Gstaiger, Matthias |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Jevtov, Irena Glatter, Timo Schittenhelm, Ralf B. Rinner, Oliver Roguska, Katarzyna Wepf, Alexander Junger, Martin A. Kohler, Katja Choi, Hyungwon Schmidt, Alexander Nesvizhskii, Alexey I. Stocker, Hugo Hafen, Ernst Aebersold, Ruedi Gstaiger, Matthias |
| author_sort | Jevtov, Irena |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:26:12Z |
| format | Article |
| id | mit-1721.1/77992 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:26:12Z |
| publishDate | 2013 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/779922022-09-28T14:13:13Z Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome Jevtov, Irena Glatter, Timo Schittenhelm, Ralf B. Rinner, Oliver Roguska, Katarzyna Wepf, Alexander Junger, Martin A. Kohler, Katja Choi, Hyungwon Schmidt, Alexander Nesvizhskii, Alexey I. Stocker, Hugo Hafen, Ernst Aebersold, Ruedi Gstaiger, Matthias Massachusetts Institute of Technology. Department of Biological Engineering Jevtov, Irena 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. 2013-03-26T18:23:38Z 2013-03-26T18:23:38Z 2011-11 2011-09 Article http://purl.org/eprint/type/JournalArticle 1744-4292 http://hdl.handle.net/1721.1/77992 Glatter, Timo et al. “Modularity and Hormone Sensitivity of the Drosophila Melanogaster Insulin Receptor/target of Rapamycin Interaction Proteome.” Molecular Systems Biology 7 (2011). en_US http://dx.doi.org/10.1038/msb.2011.79 Molecular Systems Biology Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Nature Publishing Group Molecular Systems Biology/Nature Publishing Group |
| spellingShingle | Jevtov, Irena Glatter, Timo Schittenhelm, Ralf B. Rinner, Oliver Roguska, Katarzyna Wepf, Alexander Junger, Martin A. Kohler, Katja Choi, Hyungwon Schmidt, Alexander Nesvizhskii, Alexey I. Stocker, Hugo Hafen, Ernst Aebersold, Ruedi Gstaiger, Matthias Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome |
| title | Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome |
| title_full | Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome |
| title_fullStr | Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome |
| title_full_unstemmed | Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome |
| title_short | Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome |
| title_sort | modularity and hormone sensitivity of the drosophila melanogaster insulin receptor target of rapamycin interaction proteome |
| url | http://hdl.handle.net/1721.1/77992 |
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