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.
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Hawke
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Li
authors.affiliation: The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Sadhan
authors.initials: S
authors.lastname: Majumder
authors.affiliation: Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Erfei
authors.initials: E
authors.lastname: Bi
authors.affiliation: Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA 99202, USA.
authors.forename: David X
authors.initials: DX
authors.lastname: Liu
authors.affiliation: Departments of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Suyun
authors.initials: S
authors.lastname: Huang
authors.affiliation: 1] Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [3] Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D064107:Aurora Kinase B / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D048749:Cytokinesis / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis / Q000502:physiology; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D011725:Pyridines / Q000494:pharmacology; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D000577:Amides; D064107:Aurora Kinase B; D024722:Cardiac Myosins; D002352:Carrier Proteins; D066246:ErbB Receptors; D007976:Leupeptins; D008565:Membrane Proteins; D018994:Myosin Light Chains; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D011725:Pyridines; D011770:Pyruvate Kinase; D034741:RNA, Small Interfering; D013963:Thyroid Hormones; D018631:ras Proteins; D054460:rho-Associated Kinases; D000097810:Thyroid Hormone-Binding Proteins; C117307:KRAS protein, human; C107184:myosin light chain 2; C108830:Y 27632; C512478:EGFR protein, human; C576921:AURKB protein, human; C482119:BRAF protein, human; C515852:ROCK2 protein, human; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde