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ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization

New research from Bogucka-Janczi et al. reveals a novel role for ERK3, an atypical MAPK, in controlling actin dynamics, which are essential for key cellular functions. The researchers discovered that in human cells, ERK3 directly acts as a guanine nucleotide exchange factor for CDC42 and phosphorylates the ARP3 subunit of the ARP2/3 complex, promoting filopodia formation and actin polymerization. Depletion of ERK3 halted both basal and EGF-dependent RAC1 and CDC42 activation, maintenance of F-actin content, filopodia formation, and epithelial cell migration. The ERK3 protein bound directly to the purified ARP2/3 complex and enhanced actin polymerization in vitro. The kinase activity of ERK3 was shown to be necessary for the formation of actin-rich protrusions in mammalian cells. These findings reveal a unique pathway by which cells regulate actin-dependent cellular functions​.


This study made use of the IonOpticks Aurora Ultimate 25cm column to optimize sensitivity and coverage for proteomic analysis.

Journal Article – April 2023  – eLife Sciences

Authors:

K. Bogucka-Janczi; G. Harms; M-M. Coissieux; M. Bentires-Alj; B. Thiede; K. Rajalingam

Title

ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization

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