1. Cell Biology
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ERK3/MAPK6 controls IL-8 production and chemotaxis

  1. Katarzyna Bogucka
  2. Malvika Pompaiah
  3. Federico Marini
  4. Harald Binder
  5. Gregory Harms
  6. Manuel Kaulich
  7. Matthias Klein
  8. Christian Michel
  9. Markus P Radsak
  10. Sebastian Rosigkeit
  11. Peter Grimminger
  12. Hansjörg Schild
  13. Krishnaraj Rajalingam  Is a corresponding author
  1. Johannes Gutenberg University of Mainz, Germany
  2. Goethe University Frankfurt, Germany
  3. Institute for Immunology/ University Medical Center Mainz, Germany
  4. University Medical Center of the Johannes Gutenberg University Mainz, Germany
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Cite this article as: eLife 2020;9:e52511 doi: 10.7554/eLife.52511

Abstract

ERK3 is a ubiquitously expressed member of the atypical mitogen activated protein kinases (MAPKs) and the physiological significance of its short half-life remains unclear. By employing gastrointestinal 3D organoids, we detect that ERK3 protein levels steadily decrease during epithelial differentiation. ERK3 is not required for 3D growth of human gastric epithelium. However, ERK3 is stabilized and activated in tumourigenic cells, but deteriorates over time in primary cells in response to lipopolysaccharide (LPS). ERK3 is necessary for production of several cellular factors including interleukin-8 (IL-8), in both, normal and tumourigenic cells. Particularly, ERK3 is critical for AP-1 signaling through its interaction and regulation of c-Jun protein. The secretome of ERK3 deficient cells is defective in chemotaxis of neutrophils and monocytes both in vitro and in vivo. Further, knockdown of ERK3 reduces metastatic potential of invasive breast cancer cells. We unveil an ERK3-mediated regulation of IL-8 and epithelial secretome for chemotaxis.

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Author details

  1. Katarzyna Bogucka

    Cell Biology Unit, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Malvika Pompaiah

    Cell Biology Unit, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Federico Marini

    Institute of Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3252-7758
  4. Harald Binder

    IMBEI, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Gregory Harms

    Cell Biology Unit, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Manuel Kaulich

    Institute of Biochemistry II, Goethe University Frankfurt, Frankfurt am Main, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9528-8822
  7. Matthias Klein

    Institute of Immunology, Institute for Immunology/ University Medical Center Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Christian Michel

    Department of Hematology, Medical Oncology, & Pneumology, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Markus P Radsak

    Department of Hematology, Medical Oncology, & Pneumology, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Sebastian Rosigkeit

    Cell Biology Unit, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Peter Grimminger

    Department of General, visceral and transplantation surgery, Johannes Gutenberg University of Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Hansjörg Schild

    Department of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
    Competing interests
    The authors declare that no competing interests exist.
  13. Krishnaraj Rajalingam

    Cell Biology Unit, Johannes Gutenberg University of Mainz, Mainz, Germany
    For correspondence
    krishna@uni-mainz.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4175-9633

Funding

Deutsche Forschungsgemeinschaft (RA1739/4-1)

  • Krishnaraj Rajalingam

Deutsche Forschungsgemeinschaft (CRC1292)

  • Katarzyna Bogucka

Merck KGaA (ERK-KR)

  • Krishnaraj Rajalingam

Else Kröner-Fresenius-Stiftung (SUNMAPK)

  • Malvika Pompaiah

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The animalexperiment was performed under the permission (G16-1-026) of the National Investigation Office Rheinland-Pfalz and conducted according to the German Animal Protection Law

Human subjects: Tissue samples employed are obtained from the biobank of the university medical center. Written informed consent was obtained from all patients, and the study was approved by the ethical committee at the University Medical Center of the JGU Mainz (approval # 837.100.16 (10419).

Reviewing Editor

  1. Yuting Ma, Suzhou Institute of Systems Medicine, China

Publication history

  1. Received: October 7, 2019
  2. Accepted: April 17, 2020
  3. Accepted Manuscript published: April 21, 2020 (version 1)
  4. Version of Record published: April 30, 2020 (version 2)

Copyright

© 2020, Bogucka et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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