ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization
- Johannes Gutenberg University of Mainz, Germany
- University Hospital of Basel, Switzerland
- University of Basel, Switzerland
- University of Oslo, Norway
Abstract
The actin cytoskeleton is tightly controlled by RhoGTPases, actin binding-proteins and nucleation-promoting factors to perform fundamental cellular functions. We have previously shown that ERK3, an atypical MAPK controls IL-8 production and chemotaxis52. Here, we show in human cells that, ERK3 directly acts as a guanine nucleotide exchange factor for CDC42and phosphorylates the ARP3 subunit of the ARP2/3 complex at S418 to promote filopodia formation and actin polymerization, respectively. Consistently, depletion of ERK3 prevented both basal and EGF-dependent RAC1 and CDC42 activation, maintenance of F-actin content, filopodia formation and epithelial cell migration. Further, ERK3 protein bound directly to the purified ARP2/3 complex and augmented polymerization of actin in vitro. ERK3 kinase activity was required for the formation of actin-rich protrusions in mammalian cells. These findings unveil a fundamentally unique pathway employed by cells to control actin-dependent cellular functions.
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Author details
Katarzyna Bogucka-Janczi
Mary May-Coissieux
Krishnaraj Rajalingam
Funding
Else Kröner-Fresenius-Stiftung (SUN-MAPK)
- Katarzyna Bogucka-Janczi
- Gregory Harms
Deutsche Forschungsgemeinschaft (CRC1292)
- Katarzyna Bogucka-Janczi
- Krishnaraj Rajalingam
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 animal experiments were performed as per the guideliens of University MEdical center Basel
Copyright
© 2023, Bogucka-Janczi 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 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization
eLife 12:e85167.
https://doi.org/10.7554/eLife.85167
