@article {Yu1322, author = {Yu, Yonghao and Yoon, Sang-Oh and Poulogiannis, George and Yang, Qian and Ma, Xiaoju Max and Vill{\'e}n, Judit and Kubica, Neil and Hoffman, Gregory R. and Cantley, Lewis C. and Gygi, Steven P. and Blenis, John}, title = {Phosphoproteomic Analysis Identifies Grb10 as an mTORC1 Substrate That Negatively Regulates Insulin Signaling}, volume = {332}, number = {6035}, pages = {1322--1326}, year = {2011}, doi = {10.1126/science.1199484}, publisher = {American Association for the Advancement of Science}, abstract = {The evolutionarily conserved serine-threonine kinase mammalian target of rapamycin (mTOR) plays a critical role in regulating many pathophysiological processes. Functional characterization of the mTOR signaling pathways, however, has been hampered by the paucity of known substrates. We used large-scale quantitative phosphoproteomics experiments to define the signaling networks downstream of mTORC1 and mTORC2. Characterization of one mTORC1 substrate, the growth factor receptor{\textendash}bound protein 10 (Grb10), showed that mTORC1-mediated phosphorylation stabilized Grb10, leading to feedback inhibition of the phosphatidylinositol 3-kinase (PI3K) and extracellular signal{\textendash}regulated, mitogen-activated protein kinase (ERK-MAPK) pathways. Grb10 expression is frequently down-regulated in various cancers, and loss of Grb10 and loss of the well-established tumor suppressor phosphatase PTEN appear to be mutually exclusive events, suggesting that Grb10 might be a tumor suppressor regulated by mTORC1.}, issn = {0036-8075}, URL = {https://science.sciencemag.org/content/332/6035/1322}, eprint = {https://science.sciencemag.org/content/332/6035/1322.full.pdf}, journal = {Science} }