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Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome

Glatter, Timo and Schittenhelm, Ralf B. and Rinner, Oliver and Roguska, Katarzyna and Wepf, Alexander and Jünger, Martin A. and Köhler, Katja and Jevtov, Irena and Choi, Hyungwon and Schmidt, Alexander and Nesvizhskii, Alexey I. and Stocker, Hugo and Hafen, Ernst and Aebersold, Ruedi and Gstaiger, Matthias. (2011) Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome. Molecular Systems Biology, Vol. 7 , 547.

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Official URL: http://edoc.unibas.ch/dok/A5848534

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Schmidt, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:EMBO
ISSN:1744-4292
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Sep 2012 07:19
Deposited On:14 Sep 2012 06:54

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