Proteomics

Dataset Information

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Phosphoproteomic analysis identifies supervillin as a new ERK3 substrate regulating cytokinesis and ploidy of breast cancer cells


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 potential 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 cytokinetic furrowing in dividing cells. Depletion of SVIL or ERK3 leads to 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

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Eric Bonneil  

LAB HEAD: Sylvain Meloche

PROVIDER: PXD028061 | Pride | 2023-02-21

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
ERK3_phospho_cytosol_ID1_HCD.raw Raw
ERK3_phospho_cytosol_ID2_HCD.raw Raw
ERK3_phospho_cytosol_ID3_HCD.raw Raw
ERK3_phospho_cytosol_ID4_HCD.raw Raw
ERK3_phospho_nuclei_ID1_HCD.raw Raw
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Publications

Phosphoproteomic analysis identifies supervillin as an ERK3 substrate regulating cytokinesis and cell ploidy.

Javary Joaquim J   Goupil Eugénie E   Soulez Mathilde M   Kanshin Evgeny E   Bouchard Antoine A   Seternes Ole-Morten OM   Thibault Pierre P   Labbé Jean-Claude JC   Meloche Sylvain S  

Journal of cellular physiology 20221228 3


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 i  ...[more]

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