ERK3/MAPK6 controls IL-8 production and chemotaxis
- Johannes Gutenberg University of Mainz, Germany
- Goethe University Frankfurt, Germany
- Institute for Immunology/ University Medical Center Mainz, Germany
- University Medical Center of the Johannes Gutenberg University Mainz, Germany
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.
Data availability
The RNA-seq data presented in this manuscript have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO series accession number GSE136002 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE136002)
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control vs siERK3 RNA seq analysisNCBI Gene Expression Omnibus, GSE136002.
Article and author information
Author details
Krishnaraj Rajalingam
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.
Reviewing Editor
- Yuting Ma, Suzhou Institute of Systems Medicine, China
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).
Version history
- Received: October 7, 2019
- Accepted: April 17, 2020
- Accepted Manuscript published: April 21, 2020 (version 1)
- 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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ERK3/MAPK6 controls IL-8 production and chemotaxis
eLife 9:e52511.
https://doi.org/10.7554/eLife.52511
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