ID | 112432 |
Author |
Shindo, Yuki
Osaka University|RIKEN
Iwamoto, Kazunari
RIKEN
Mouri, Kazunari
RIKEN
Hibino, Kayo
RIKEN
Tomita, Masaru
Keio University
Kosako, Hidetaka
Tokushima University
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Sako, Yasushi
RIKEN
Takahashi, Koichi
RIKEN|Keio University
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Content Type |
Journal Article
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Description | 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.
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Journal Title |
Nature Communications
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ISSN | 20411723
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NCID | AA12645905
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Publisher | Springer Nature
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Volume | 7
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Start Page | 10485
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Published Date | 2016-01-20
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Remark | Supplementary Information : ncomms_7_10485_s1.pdf
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Rights | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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DOI (Published Version) | |
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language |
eng
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TextVersion |
Publisher
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departments |
Institute of Advanced Medical Sciences
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