Chemical genetic screen for AMPKα2 substrates uncovers a network of proteins involved in mitosis.
Chemical genetic screen for AMPKα2 substrates uncovers a network of proteins involved in mitosis.
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DOI：
10.1016/j.molcel.2011.11.005
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发表时间：
2011-12-23
期刊：
影响因子：
16
通讯作者：
Brunet, Anne
中科院分区：
文献类型：
--
作者：
Banko, Max R.;Allen, Jasmina J.;Schaffer, Bethany E.;Wilker, Erik W.;Tsou, Peiling;White, Jamie L.;Villen, Judit;Wang, Beatrice;Kim, Sara R.;Sakamoto, Kei;Gygi, Steven P.;Cantley, Lewis C.;Yaffe, Michael B.;Shokat, Kevan M.;Brunet, Anne
能量敏感AMP激活蛋白激酶（AMPK）被低营养水平激活。AMPK的功能，除了它在细胞代谢中的作用，才刚刚开始出现。在这里，我们使用化学遗传学筛选，以确定人类细胞中AMPK的直接底物。我们发现AMPK磷酸化28个以前未鉴定的底物，其中几个参与有丝分裂和胞质分裂。我们在体内鉴定了AMPK在几种底物中磷酸化的残基，包括蛋白磷酸酶1调节亚基12 C（PPP 1 R12 C）和p21激活的蛋白激酶（PAK 2）。AMPK诱导的磷酸化是PPP 1 R12 C与14-3-3相互作用和肌球蛋白调节轻链磷酸化所必需的。AMPK活性和PPP 1 R12 C磷酸化在有丝分裂细胞中增加，并且对于有丝分裂完成是重要的。这些发现表明AMPK协调营养状态与有丝分裂完成，这可能是生物体在发育过程中或成体干细胞和癌细胞中对低营养的反应的关键。
The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. Here we use a chemical genetics screen to identify direct substrates of AMPK in human cells. We find that AMPK phosphorylates 28 previously unidentified substrates, several of which are involved in mitosis and cytokinesis. We identify the residues phosphorylated by AMPK in vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21 -activated protein kinase (PAK2). AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both AMPK activity and PPP1R12C phosphorylation are increased in mitotic cells and are important for mitosis completion. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism’s response to low nutrients during development, or in adult stem and cancer cells.
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影响因子：
11.8
作者：
Dasgupta, Biplab;Milbrandt, Jeffrey
通讯作者：
Milbrandt, Jeffrey
影响因子：
3.7
作者：
Brennan IM;Peters U;Kapoor TM;Straight AF
通讯作者：
Straight AF
DOI：
10.1073/pnas.0708966105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Blethrow, Justin D.;Glavy, Joseph S.;Shokat, Kevan M.
通讯作者：
Shokat, Kevan M.
DOI：
10.1006/bbrc.2001.5627
发表时间：
2001-09-21
影响因子：
3.1
作者：
Imamura, K;Ogura, T;Esumi, H
通讯作者：
Esumi, H
影响因子：
16
作者：
Jones, RG;Plas, DR;Thompson, CB
通讯作者：
Thompson, CB