PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells.
PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells.
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DOI：
10.1038/ncomms6566
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发表时间：
2014-11-21
影响因子：
16.6
通讯作者：
Lu, Zhimin
中科院分区：
文献类型：
--
作者：
Jiang, Yuhui;Wang, Yugang;Wang, Ting;Hawke, David H.;Zheng, Yanhua;Li, Xinjian;Zhou, Qin;Majumder, Sadhan;Bi, Erfei;Liu, David X.;Huang, Suyun;Lu, Zhimin
丙酮酸激酶M2（PKM 2）在胚胎发育和肿瘤进展过程中高水平表达，对细胞生长至关重要。但是，目前还不清楚它是否直接控制细胞分裂。在这里，我们发现极光B磷酸化PKM 2，但不是PKM 1，在T45，这种磷酸化是PKM 2的本地化和相互作用所需的肌球蛋白轻链2（MLC 2）在收缩环区域的有丝分裂细胞在胞质分裂。PKM 2在Y118处磷酸化MLC 2，这引发ROCK 2与MLC 2的结合以及随后的ROCK 2依赖性MLC 2 S15磷酸化。PKM 2调节的MLC 2磷酸化在胞质分裂、细胞增殖和脑肿瘤发展中起关键作用，其通过EGF刺激或EGFRvIII、K-Ras G12 V和B-Raf V600 E突变体表达而大大增强。这些发现强调了PKM 2在致癌EGFR、K-Ras和B-Raf调节的胞质分裂和肿瘤发生中的工具性功能。
Pyruvate kinase M2 (PKM2) is expressed at high levels during embryonic development and tumor progression and is important for cell growth. However, it is not known whether it directly controls cell division. Here, we found that Aurora B phosphorylates PKM2, but not PKM1, at T45; this phosphorylation is required for PKM2's localization and interaction with myosin light chain 2 (MLC2) in the contractile ring region of mitotic cells during cytokinesis. PKM2 phosphorylates MLC2 at Y118, which primes the binding of ROCK2 to MLC2 and subsequent ROCK2-dependent MLC2 S15 phosphorylation. PKM2-regulated MLC2 phosphorylation, which is greatly enhanced by EGF stimulation or EGFRvIII, K-Ras G12V, and B-Raf V600E mutant expression, plays a pivotal role in cytokinesis, cell proliferation, and brain tumor development. These findings underscore the instrumental function of PKM2 in oncogenic EGFR-, K-Ras-, and B-Raf-regulated cytokinesis and tumorigenesis.
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影响因子：
16
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
通讯作者：
Brunet, Anne
DOI：
10.1126/science.1211485
发表时间：
2011-12-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Anastasiou D;Poulogiannis G;Asara JM;Boxer MB;Jiang JK;Shen M;Bellinger G;Sasaki AT;Locasale JW;Auld DS;Thomas CJ;Vander Heiden MG;Cantley LC
通讯作者：
Cantley LC
影响因子：
11.4
作者：
Lowery, Drew M.;Clauser, Karl R.;Yaffe, Michael B.
通讯作者：
Yaffe, Michael B.
影响因子：
64.5
作者：
Hsu, Peggy P.;Sabatini, David M.
通讯作者：
Sabatini, David M.
影响因子：
4.8
作者：
Goto, H;Yasui, Y;Inagaki, M
通讯作者：
Inagaki, M