PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells

Yuhui Jiang; Yugang Wang; Ting Wang; David H. Hawke; Yanhua Zheng; Xinjian Li; Qin Zhou; Sadhan Majumder; Erfei Bi; David X. Liu; Suyun Huang; Zhimin Lu

doi:10.1038/ncomms6566

PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells

Yuhui Jiang, Yugang Wang, Ting Wang, David H. Hawke, Yanhua Zheng, Xinjian Li, Qin Zhou, Sadhan Majumder, Erfei Bi, David X. Liu, Suyun Huang, Zhimin Lu

Research output: Contribution to journal › Article › peer-review

105 Scopus citations

Abstract

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.

Original language	English (US)
Article number	5566
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6566
State	Published - 2014

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms6566

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title = "PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells",

abstract = "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.",

author = "Yuhui Jiang and Yugang Wang and Ting Wang and Hawke, {David H.} and Yanhua Zheng and Xinjian Li and Qin Zhou and Sadhan Majumder and Erfei Bi and Liu, {David X.} and Suyun Huang and Zhimin Lu",

note = "Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited.",

year = "2014",

doi = "10.1038/ncomms6566",

language = "English (US)",

volume = "5",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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T1 - PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells

AU - Jiang, Yuhui

AU - Wang, Yugang

AU - Wang, Ting

AU - Hawke, David H.

AU - Zheng, Yanhua

AU - Li, Xinjian

AU - Zhou, Qin

AU - Majumder, Sadhan

AU - Bi, Erfei

AU - Liu, David X.

AU - Huang, Suyun

AU - Lu, Zhimin

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms6566

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JO - Nature communications

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PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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