Article ; Online: Phosphoproteomic analysis identifies supervillin as an ERK3 substrate regulating cytokinesis and cell ploidy.
Journal of cellular physiology
2022 Volume 239, Issue 3, Page(s) e30938
Abstract: Extracellular signal-regulated kinase 3 (ERK3) is a poorly characterized member of the mitogen-activated protein (MAP) kinase family. Functional analysis of the ERK3 signaling pathway has been hampered by a lack of knowledge about the substrates and ... ...
Abstract | Extracellular signal-regulated kinase 3 (ERK3) is a poorly characterized member of the mitogen-activated protein (MAP) kinase family. Functional analysis of the ERK3 signaling pathway has been hampered by a lack of knowledge about the substrates and downstream effectors of the kinase. Here, we used large-scale quantitative phosphoproteomics and targeted gene silencing to identify direct ERK3 substrates and gain insight into its cellular functions. Detailed validation of one candidate substrate identified the gelsolin/villin family member supervillin (SVIL) as a bona fide ERK3 substrate. We show that ERK3 phosphorylates SVIL on Ser245 to regulate myosin II activation and cytokinesis completion in dividing cells. Depletion of SVIL or ERK3 leads to increased cytokinesis failure and multinucleation, a phenotype rescued by wild type SVIL but not by the non-phosphorylatable S245A mutant. Our results unveil a new function of the atypical MAP kinase ERK3 in cell division and the regulation of cell ploidy. |
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MeSH term(s) | Cytokinesis/genetics ; Mitogen-Activated Protein Kinase 6/metabolism ; Signal Transduction ; Phosphorylation ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Microfilament Proteins/genetics ; Microfilament Proteins/metabolism ; Myosin Type II/metabolism ; Humans ; HEK293 Cells ; Animals ; Proteomics |
Chemical Substances | Mitogen-Activated Protein Kinase 6 (EC 2.7.11.24) ; SVIL protein, human ; Membrane Proteins ; Microfilament Proteins ; Myosin Type II (EC 3.6.1.-) |
Language | English |
Publishing date | 2022-12-28 |
Publishing country | United States |
Document type | Journal Article |
ZDB-ID | 3116-1 |
ISSN | 1097-4652 ; 0021-9541 |
ISSN (online) | 1097-4652 |
ISSN | 0021-9541 |
DOI | 10.1002/jcp.30938 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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