Authors:	Bogucka-Janczi, Katarzyna Harms, Gregory Coissieux, Marie-May Bentires-Alj, Mohamed Thiede, Bernd Rajalingam, Krishnaraj
Title:	ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization
Online publication date:	8-Aug-2023
Year of first publication:	2023
Language:	english
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 chemotaxis (Bogueka et al., 2020). Here, we show in human cells that ERK3 directly acts as a guanine nucleotide exchange factor for CDC42 and 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.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9348
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	eLife 12
Pages or article number:	e85167
Publisher:	eLife Sciences Publications
Publisher place:	Cambridge
Issue date:	2023
ISSN:	2050-084X
Publisher DOI:	10.7554/eLife.85167
Appears in collections:	DFG-491381577-G