PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells

被引：122

作者：

Jiang, Yuhui ^{[1
,2
]}

Wang, Yugang ^{[1
,2
]}

Wang, Ting ^{[3
]}

Hawke, David H. ^{[4
]}

Zheng, Yanhua ^{[1
,2
]}

Li, Xinjian ^{[1
,2
]}

Zhou, Qin ^{[5
]}

Majumder, Sadhan ^{[6
]}

Bi, Erfei ^{[3
]}

Liu, David X. ^{[7
]}

Huang, Suyun ^{[8
]}

Lu, Zhimin ^{[1
,2
,9
,10
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Brain Tumor Ctr, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA

[3] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[5] Chongqing Med Univ, Coll Lab Med, MOE Key Lab Lab Med Diagnost, Chongqing 400016, Peoples R China

[6] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA

[7] Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Spokane, WA USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[10] Univ Texas Houston, Grad Sch Biomed Sci Houston, Canc Biol Program, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

PYRUVATE-KINASE M2; LIGHT-CHAIN PHOSPHORYLATION; GENE-TRANSCRIPTION; BETA-CATENIN; PROMOTES; ISOFORM; DEGRADATION; INHIBITION; METABOLISM; ACTIVATION;

D O I：

10.1038/ncomms6566

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pyruvate kinase M2 (PKM2) is expressed at high levels during embryonic development and tumour 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 tumour development. These findings underscore the instrumental function of PKM2 in oncogenic EGFR- ,K-Ras- and B-Raf-regulated cytokinesis and tumorigenesis.

引用

页数：14

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