Dynamic Regulation of Extracellular Signal-Regulated Kinase by Protein Phosphatase 2A Regulatory Subunit B56[gamma]1 in Nuclei Induces Cell Migration

• Published in: PloS one 2013-05, Vol.8 (5), p.e63729
• Main Authors: Kawahara, Ei, Maenaka, Shiori, Shimada, Eri, Nishimura, Yoshihiro, Sakurai, Hiroshi
• Format: Article
• Language: English
• Subjects: Collagen; Epidermal growth factors; Phosphatases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063729

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, B56[gamma]1 suppressed EGF-induced cell migration on collagen, bound to phosphorylated-ERK, and dephosphorylated ERK, whereas B56[alpha]1 and B56[beta]1 did not. B56[gamma]1 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-B56[gamma]1 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-B56[gamma]1 through two independent pathways.