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Inactivation of ERK accelerates erythroid differentiation of K562 cells induced by herbimycin A and STI571 while activation of MEK1 interferes with it

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Abstract

K562 cells contain a Bcr-Abl chimeric gene and differentiate into various lineages in response to different inducers. We studied the role of the mitogen-activated protein kinase (MAPK) kinase 1 (MEK1)/extracellular signal-regulated kinase (ERK) pathway during the erythroid differentiation of K562 cells induced by tyrosine kinase inhibitors (herbimycin A or STI571), using genetically modified cells (constitutively MEK1-activated K562: K562/MEK1, and inducible ERK-inactivated K562: K562/CL100). Basal expression of glycophorin A was markedly reduced in K562/MEK1 cells compared with that in parental cells, while it was augmented in K562/CL100 cells. Herbimycin A and STI571 differentiated K562 cells accompanying with the transient down-regulated ERK. Moreover, the erythroid differentiation was markedly suppressed in K562/MEK1 cells, and early down-regulation of ERK activity was not observed in these cells. In contrast, the induction of ERK-specific phosphatase in K562/CL100 cells potentiated erythroid differentiation. Once the phosphatase was induced, the initial ERK activity became repressed and its early down-regulation by the inhibition of Bcr-Abl was marked and prolonged. These results demonstrate that the erythroid differentiation of K562 cells induced by herbimycin A or STI571 requires the down-regulation of MEK1/ERK pathway.

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Authors and Affiliations

  1. Department of Molecular Genetics, Institute of DNA Medicine, Jikei University School of Medicine, Nishi-Shinbashi 3-25-8, Minato-ku, Tokyo, 105-8461, Japan

    Takeshi Kawano, Satsuki Iwase & Hisashi Yamada

  2. Department of Oncology, Institute of DNA Medicine, Jikei University School of Medicine, Nishi-Shinbashi 3-25-8, Minato-ku, Tokyo, 105-8461, Japan

    Junko Horiguchi-Yamada

  3. Division of Molecular Hematopoiesis and Molecular Biology, Jichi Medical School, Tochigi, Japan

    Yusuke Furukawa

  4. Division of Hematology and Medical Oncology, Tochigi Cancer Center, Tochigi, Japan

    Yasuhiko Kano

Authors
  1. Takeshi Kawano
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  2. Junko Horiguchi-Yamada
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  3. Satsuki Iwase
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  4. Yusuke Furukawa
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  5. Yasuhiko Kano
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  6. Hisashi Yamada
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Kawano, T., Horiguchi-Yamada, J., Iwase, S. et al. Inactivation of ERK accelerates erythroid differentiation of K562 cells induced by herbimycin A and STI571 while activation of MEK1 interferes with it. Mol Cell Biochem 258, 25–33 (2004). https://doi.org/10.1023/B:MCBI.0000012830.96393.b9

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  • DOI: https://doi.org/10.1023/B:MCBI.0000012830.96393.b9

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