Conversion of graded phosphorylation into switch-like nuclear translocation via autoregulatory mechanisms in ERK signalling

Yuki Shindo, Kazunari Iwamoto, Kazunari Mouri, Kayo Hibino, Masaru Tomita, Hidetaka Kosako, Yasushi Sako, Koichi Takahashi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The phosphorylation cascade in the extracellular signal-regulated kinase (ERK) pathway is a versatile reaction network motif that can potentially act as a switch, oscillator or memory. Nevertheless, there is accumulating evidence that the phosphorylation response is mostly linear to extracellular signals in mammalian cells. Here we find that subsequent nuclear translocation gives rise to a switch-like increase in nuclear ERK concentration in response to signal input. The switch-like response disappears in the presence of ERK inhibitor, suggesting the existence of autoregulatory mechanisms for ERK nuclear translocation involved in conversion from a graded to a switch-like response. In vitro reconstruction of ERK nuclear translocation indicates that ERK-mediated phosphorylation of nucleoporins regulates ERK translocation. A mathematical model and knockdown experiments suggest a contribution of nucleoporins to regulation of the ERK nuclear translocation response. Taken together, this study provides evidence that nuclear translocation with autoregulatory mechanisms acts as a switch in ERK signalling.

Original languageEnglish
Article number10485
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 2016 Jan 20

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phosphorylation
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
switches
Switches
Nuclear Pore Complex Proteins
Theoretical Models
inhibitors
Cells
Mathematical models
mathematical models
cascades
Data storage equipment
oscillators

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Conversion of graded phosphorylation into switch-like nuclear translocation via autoregulatory mechanisms in ERK signalling. / Shindo, Yuki; Iwamoto, Kazunari; Mouri, Kazunari; Hibino, Kayo; Tomita, Masaru; Kosako, Hidetaka; Sako, Yasushi; Takahashi, Koichi.

In: Nature Communications, Vol. 7, 10485, 20.01.2016.

Research output: Contribution to journalArticle

Shindo, Yuki ; Iwamoto, Kazunari ; Mouri, Kazunari ; Hibino, Kayo ; Tomita, Masaru ; Kosako, Hidetaka ; Sako, Yasushi ; Takahashi, Koichi. / Conversion of graded phosphorylation into switch-like nuclear translocation via autoregulatory mechanisms in ERK signalling. In: Nature Communications. 2016 ; Vol. 7.
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