Functional Proteomics Identifies Acinus L as a Direct Insulin- and Amino Acid-Dependent Mammalian Target of Rapamycin Complex 1 (mTORC1) SubstrateSchwarz, J. J., Wiese, H., Toelle, R. C., Zarei, M., Dengjel, J., Warscheid, B. & Thedieck, K., Aug-2015, In : Molecular & Cellular Proteomics. 14, 8, p. 2042-2055 14 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||14|
|Journal||Molecular & Cellular Proteomics|
|Publication status||Published - Aug-2015|
- NOVO PYRIMIDINE SYNTHESIS, EXON JUNCTION COMPLEX, RICH AKT SUBSTRATE, P70 S6 KINASE, 40 KDA PRAS40, CELL-GROWTH, CHROMATIN CONDENSATION, MOTIF PHOSPHORYLATION, SIGNAL INTEGRATION, BINDING PARTNER
Biomedical datasets to: Functional proteomics identifies acinus L as a direct insulin- and amino acid-dependent mTORC1 substrate
Schwarz, J. J. (Creator), Wiese, H. (Creator), Tölle, R. C. (Creator), Zarei, M. (Creator), Dengjel, J. (Creator), Warscheid, B. (Creator), Thedieck, K. (Creator), European Bioinformatics Institute (EMBL-EBI), 28-Apr-2015