Functional Proteomics Identifies Acinus L as a Direct Insulin- and Amino Acid-Dependent Mammalian Target of Rapamycin Complex 1 (mTORC1) Substrate*
Functional Proteomics Identifies Acinus L as a Direct Insulin- and Amino Acid-Dependent Mammalian Target of Rapamycin Complex 1 (mTORC1) Substrate*
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功能蛋白质组学将 Acinus L 确定为雷帕霉素复合物 1 (mTORC1) 底物的直接胰岛素和氨基酸依赖性哺乳动物靶标*
DOI：
10.1074/mcp.m114.045807
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发表时间：
2015
影响因子：
7
通讯作者：
Thedieck K
中科院分区：
文献类型：
--
作者：
Schwarz J;Wiese H;Tölle RC;Zarei M;Dengjel J;Warscheid B;Thedieck K
丝氨酸/苏氨酸激酶哺乳动物雷帕霉素靶标（mTOR）响应于胰岛素和氨基酸（aa）控制生长、代谢和衰老，并且通常在代谢紊乱和癌症中被激活。关于包含mTOR的调节信号网络已知很多，但令人惊讶的是，迄今为止很少建立直接的mTOR底物。为了解决我们知识中的这一差距，我们利用了定量磷酸蛋白质组学和相互作用组学相结合的策略。我们分析了胰岛素和aa-响应磷酸化蛋白质组后，抑制mTOR复合物1（mTORC 1）组件猛禽，并平行研究内源性mTOR的相互作用。通过覆盖这两个数据集，我们将腺泡L确定为潜在的新型mTORC 1靶点。我们证实腺泡L作为直接mTORC 1底物的免疫共沉淀和MS增强激酶测定。我们的研究描绘了磷酸化蛋白质组学、相互作用组学和MS增强激酶测定相结合的三重蛋白质组学策略，用于mTOR网络组分的从头鉴定，并为未来的研究提供了潜在的新型mTOR相互作用物和靶点的丰富来源。
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 thede novo-identification of mTOR network components, and provides a rich source of potential novel mTOR interactors and targets for future investigation.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
7.3
作者：
Pezze, Piero Dalle;Sonntag, Annika G.;Thedieck, Kathrin
通讯作者：
Thedieck, Kathrin
DOI：
10.1016/s0021-9258(19)61974-5
发表时间：
1994-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. G. Myers;T. Grammer;Ling-mei Wang;X. Sun;J. Pierce;J. Blenis;M. White
通讯作者：
M. G. Myers;T. Grammer;Ling-mei Wang;X. Sun;J. Pierce;J. Blenis;M. White
影响因子：
16
作者：
Sarbassov, DD;Ali, SM;Sabatini, DM
通讯作者：
Sabatini, DM
影响因子：
56.9
作者：
Brunn, GJ;Hudson, CC;Abraham, RT
通讯作者：
Abraham, RT