title: Dynamic regulation of extracellular signal-regulated kinase (ERK) by protein phosphatase 2A regulatory subunit B56γ1 in nuclei induces cell migration.
abstract: Extracellular signal-regulated kinase (ERK) signalling plays a central role in various biological processes, including cell migration, but it remains unknown what factors directly regulate the strength and duration of ERK activation. We found that, among the B56 family of protein phosphatase 2A (PP2A) regulatory subunits, B56γ1 suppressed EGF-induced cell migration on collagen, bound to phosphorylated-ERK, and dephosphorylated ERK, whereas B56α1 and B56β1 did not. B56γ1 was immunolocalized in nuclei. The IER3 protein was immediately highly expressed in response to costimulation of cells with EGF and collagen. Knockdown of IER3 inhibited cell migration and enhanced dephosphorylation of ERK. Analysis of the time course of PP2A-B56γ1 activity following the costimulation showed an immediate loss of phosphatase activity, followed by a rapid increase in activity, and this activity then remained at a stable level that was lower than the original level. Our results indicate that the strength and duration of the nuclear ERK activation signal that is initially induced by ERK kinase (MEK) are determined at least in part by modulation of the phosphatase activity of PP2A-B56γ1 through two independent pathways.
authors.affiliation: Department of Clinical Laboratory Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Ei
authors.initials: E
authors.lastname: Kawahara
authors.forename: Shiori
authors.initials: S
authors.lastname: Maenaka
authors.forename: Eri
authors.initials: E
authors.lastname: Shimada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology*; D003094:Collagen / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D008565:Membrane Proteins; D004815:Epidermal Growth Factor; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C485589:Ppp2r5c protein, mouse; D054648:Protein Phosphatase 2