title: Modularity and hormone sensitivity of the Drosophila melanogaster insulin receptor/target of rapamycin interaction proteome.
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.
authors: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors: Timo
authors: T
authors: Glatter
authors: Ralf B
authors: RB
authors: Schittenhelm
authors: Oliver
authors: O
authors: Rinner
authors: Katarzyna
authors: K
authors: Roguska
authors: Alexander
authors: A
authors: Wepf
authors: Martin A
authors: MA
authors: Jünger
authors: Katja
authors: K
authors: Köhler
authors: Irena
authors: I
authors: Jevtov
authors: Hyungwon
authors: H
authors: Choi
authors: Alexander
authors: A
authors: Schmidt
authors: Alexey I
authors: AI
authors: Nesvizhskii
authors: Hugo
authors: H
authors: Stocker
authors: Ernst
authors: E
authors: Hafen
authors: Ruedi
authors: R
authors: Aebersold
authors: Matthias
authors: M
authors: Gstaiger
mesh_terms: D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013058:Mass Spectrometry; D060066:Protein Interaction Maps; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D020543:Proteome; D014157:Transcription Factors; D011494:Protein Kinases; C416303:target of rapamycin protein, Drosophila; D011972:Receptor, Insulin; D058570:TOR Serine-Threonine Kinases