mTORC1型
mTORC2型
磷酸蛋白质组学
PTEN公司
PI3K/AKT/mTOR通路
GRB10型
信号转导
细胞生物学
激酶
生物
MAPK/ERK通路
胰岛素受体
蛋白激酶A
癌症研究
蛋白质磷酸化
胰岛素
胰岛素抵抗
内分泌学
作者
Yonghao Yu,Sang-Oh Yoon,George Poulogiannis,Qian Yang,Xiaoju Max,Judit Villén,Neil Kubica,Gregory R. Hoffman,Lewis C. Cantley,Steven P. Gygi,John Blenis
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2011-06-10
卷期号:332 (6035): 1322-1326
被引量:806
标识
DOI:10.1126/science.1199484
摘要
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-bound protein 10 (Grb10), showed that mTORC1-mediated phosphorylation stabilized Grb10, leading to feedback inhibition of the phosphatidylinositol 3-kinase (PI3K) and extracellular signal-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.
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