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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Molecular Biology Organization
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261712/ https://www.ncbi.nlm.nih.gov/pubmed/22068330 http://dx.doi.org/10.1038/msb.2011.79 |
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author | Glatter, Timo Schittenhelm, Ralf B Rinner, Oliver Roguska, Katarzyna Wepf, Alexander Jünger, Martin A Köhler, Katja Jevtov, Irena Choi, Hyungwon Schmidt, Alexander Nesvizhskii, Alexey I Stocker, Hugo Hafen, Ernst Aebersold, Ruedi Gstaiger, Matthias |
author_facet | Glatter, Timo Schittenhelm, Ralf B Rinner, Oliver Roguska, Katarzyna Wepf, Alexander Jünger, Martin A Köhler, Katja Jevtov, Irena Choi, Hyungwon Schmidt, Alexander Nesvizhskii, Alexey I Stocker, Hugo Hafen, Ernst Aebersold, Ruedi Gstaiger, Matthias |
author_sort | Glatter, Timo |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3261712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | European Molecular Biology Organization |
record_format | MEDLINE/PubMed |
spelling | pubmed-32617122012-01-20 Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome Glatter, Timo Schittenhelm, Ralf B Rinner, Oliver Roguska, Katarzyna Wepf, Alexander Jünger, Martin A Köhler, Katja Jevtov, Irena Choi, Hyungwon Schmidt, Alexander Nesvizhskii, Alexey I Stocker, Hugo Hafen, Ernst Aebersold, Ruedi Gstaiger, Matthias Mol Syst Biol Article 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. European Molecular Biology Organization 2011-11-08 /pmc/articles/PMC3261712/ /pubmed/22068330 http://dx.doi.org/10.1038/msb.2011.79 Text en Copyright © 2011, EMBO and Macmillan Publishers Limited https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission. |
spellingShingle | Article Glatter, Timo Schittenhelm, Ralf B Rinner, Oliver Roguska, Katarzyna Wepf, Alexander Jünger, Martin A Köhler, Katja Jevtov, Irena 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261712/ https://www.ncbi.nlm.nih.gov/pubmed/22068330 http://dx.doi.org/10.1038/msb.2011.79 |
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