%0 Journal Article %1 schwarzFunctionalProteomicsIdentifies2015a %A Schwarz, Jennifer Jasmin %A Wiese, Heike %A Tölle, Regine Charlotte %A Zarei, Mostafa %A Dengjel, Jörn %A Warscheid, Bettina %A Thedieck, Kathrin %C United States %D 2015 %J Molecular & cellular proteomics : MCP %K 1,Molecular Acid Acids/*metabolism,Gene Adaptor Cells,Humans,Insulin/*metabolism,Mechanistic Complex Complexes/*metabolism,Nuclear Data,Multiprotein Interaction Kinases/*metabolism Knockdown Mapping,Proteome/metabolism,Proteomics/*methods,Regulatory-Associated Protein Proteins Proteins/chemistry/*metabolism,Phosphoproteins/metabolism,Phosphorylation,Protein Rapamycin Sequence Sequence,Amino Serine-Threonine Signal Specificity,to_read,TOR Target Techniques,HeLa Transducing/metabolism,Amino mTOR,Substrate of %N 8 %P 2042--2055 %R 10.1074/mcp.M114.045807 %T Functional Proteomics Identifies Acinus L as a Direct Insulin- and Amino Acid-Dependent Mammalian Target of Rapamycin Complex 1 (mTORC1) Substrate. %V 14 %X The serine/threonine kinase mammalian target of rapamycin (mTOR) governs growth, metabolism, and aging in response to insulin and amino acids (aa), and is often activated in metabolic disorders and cancer. Much is known about the regulatory signaling network that encompasses mTOR, but surprisingly few direct mTOR substrates have been established to date. To tackle this gap in our knowledge, we took advantage of a combined quantitative phosphoproteomic and interactomic strategy. We analyzed the insulin- and aa-responsive phosphoproteome upon inhibition of the mTOR complex 1 (mTORC1) component raptor, and investigated in parallel the interactome of endogenous mTOR. By overlaying these two datasets, we identified acinus L as a potential novel mTORC1 target. We confirmed acinus L as a direct mTORC1 substrate by co-immunoprecipitation and MS-enhanced kinase assays. Our study delineates a triple proteomics strategy of combined phosphoproteomics, interactomics, and MS-enhanced kinase assays for the de novo-identification of mTOR network components, and provides a rich source of potential novel mTOR interactors and targets for future investigation.

@article{schwarzFunctionalProteomicsIdentifies2015a, abstract = {The serine/threonine kinase mammalian target of rapamycin (mTOR) governs growth, metabolism, and aging in response to insulin and amino acids (aa), and is often activated in metabolic disorders and cancer. Much is known about the regulatory signaling network that encompasses mTOR, but surprisingly few direct mTOR substrates have been established to date. To tackle this gap in our knowledge, we took advantage of a combined quantitative phosphoproteomic and interactomic strategy. We analyzed the insulin- and aa-responsive phosphoproteome upon inhibition of the mTOR complex 1 (mTORC1) component raptor, and investigated in parallel the interactome of endogenous mTOR. By overlaying these two datasets, we identified acinus L as a potential novel mTORC1 target. We confirmed acinus L as a direct mTORC1 substrate by co-immunoprecipitation and MS-enhanced kinase assays. Our study delineates a triple proteomics strategy of combined phosphoproteomics, interactomics, and MS-enhanced kinase assays for the de novo-identification of mTOR network components, and provides a rich source of potential novel mTOR interactors and targets for future investigation.}, added-at = {2024-05-17T13:01:35.000+0200}, address = {United States}, author = {Schwarz, Jennifer Jasmin and Wiese, Heike and T{\"o}lle, Regine Charlotte and Zarei, Mostafa and Dengjel, J{\"o}rn and Warscheid, Bettina and Thedieck, Kathrin}, biburl = {https://www.bibsonomy.org/bibtex/208cc81a3fab73a622cce5bc42c39c23d/warscheidlab}, copyright = {{\copyright} 2015 by The American Society for Biochemistry and Molecular Biology, Inc.}, doi = {10.1074/mcp.M114.045807}, interhash = {cd8c90a3f2810b982bc6359745223c75}, intrahash = {08cc81a3fab73a622cce5bc42c39c23d}, issn = {1535-9484 1535-9476}, journal = {Molecular \& cellular proteomics : MCP}, keywords = {1,Molecular Acid Acids/*metabolism,Gene Adaptor Cells,Humans,Insulin/*metabolism,Mechanistic Complex Complexes/*metabolism,Nuclear Data,Multiprotein Interaction Kinases/*metabolism Knockdown Mapping,Proteome/metabolism,Proteomics/*methods,Regulatory-Associated Protein Proteins Proteins/chemistry/*metabolism,Phosphoproteins/metabolism,Phosphorylation,Protein Rapamycin Sequence Sequence,Amino Serine-Threonine Signal Specificity,to_read,TOR Target Techniques,HeLa Transducing/metabolism,Amino mTOR,Substrate of}, langid = {english}, month = aug, number = 8, pages = {2042--2055}, pmcid = {PMC4528236}, pmid = {25907765}, timestamp = {2024-05-17T13:01:35.000+0200}, title = {Functional {{Proteomics Identifies Acinus L}} as a {{Direct Insulin-}} and {{Amino Acid-Dependent Mammalian Target}} of {{Rapamycin Complex}} 1 ({{mTORC1}}) {{Substrate}}.}, volume = 14, year = 2015 }