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

Nature Communications
Yuki ShindoKoichi Takahashi

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.

References

Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·C Y Huang, J E Ferrell
Mar 10, 2001·Nature·L Chang, M Karin
Nov 13, 2001·Developmental Cell·E FormstecherH Chneiweiss
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Angelique W WhitehurstMelanie H Cobb
Apr 23, 2003·Experimental Cell Research·Angela M Horgan, Philip J S Stork
Jan 28, 2004·The Journal of Cell Biology·Nick I MarkevichBoris N Kholodenko
Jul 9, 2004·Developmental Cell·Satoru ToriiEisuke Nishida
May 19, 2005·Molecular and Cellular Biology·Jeffrey P MackeiganJohn Blenis
Aug 18, 2005·Journal of Cell Science·Maosong Qi, Elaine A Elion
Sep 6, 2005·Biochemical and Biophysical Research Communications·Makoto OhoriTakashi Fujii
Nov 16, 2006·Journal of Cell Science·Mario CostaGian Michele Ratto
Feb 21, 2007·Nature Cell Biology·Silvia D M SantosPhilippe I H Bastiaens
Oct 3, 2007·PLoS Computational Biology·Liang QiaoStanislav Y Shvartsman
Sep 22, 2009·Nature Structural & Molecular Biology·Hidetaka KosakoSeisuke Hattori
Dec 17, 2009·Molecular Cell·Cellina Cohen-SaidonUri Alon
Jan 19, 2010·Biochimica Et Biophysica Acta·Eun Kyung Kim, Eui-Ju Choi
Jul 16, 2010·Cold Spring Harbor Perspectives in Biology·Susan R Wente, Michael P Rout
Aug 21, 2010·The Journal of Biological Chemistry·Yuji KamiokaMichiyuki Matsuda
Jul 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kazuhiro AokiMichiyuki Matsuda
Sep 17, 2011·Science·Raymond CheongAndre Levchenko
Jan 21, 2012·Biochemical Society Transactions·Christopher J Caunt, Craig A McArdle
May 1, 2012·Biochemical and Biophysical Research Communications·Masahiro TakahashiYasushi Sako
Sep 23, 2014·Trends in Biochemical Sciences·James E Ferrell, Sang Hoon Ha
Mar 31, 2015·Nature Communications·Alexander PlotnikovRony Seger

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Citations

Jul 5, 2016·Frontiers in Cell and Developmental Biology·Roser BuscàPhilippe Lenormand
May 27, 2016·Molecular Biology of the Cell·Boris Y RubinsteinStanislav Y Shvartsman
Aug 16, 2017·Physical Chemistry Chemical Physics : PCCP·Anna Ochab-MarcinekMarcin Tabaka
Jul 4, 2018·Journal of Cell Science·Cédric YapoLiliana R V Castro
Oct 3, 2018·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Sonal ManoharGanesh Viswanathan
Mar 10, 2019·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yosuke OguraShigeo Hayashi
Sep 29, 2019·Nature Communications·Taylor M Courtney, Alexander Deiters
Jun 14, 2019·Molecular Carcinogenesis·Rachel M SammonsKevin N Dalby
Feb 2, 2019·International Journal of Molecular Sciences·Ankur MishraPatrick R Onck
Jan 8, 2021·PLoS Computational Biology·Jan Rombouts, Lendert Gelens
Apr 29, 2021·Computers in Biology and Medicine·Manuel JuradoAntonio Zorzano
May 4, 2021·Frontiers in Cell and Developmental Biology·Makoto NasuKenji Shimamura
Oct 7, 2020·Ecotoxicology and Environmental Safety·Zhiwen YangGuimiao Lin
Nov 5, 2021·Frontiers in Oncology·Yuqi XiaDi Zheng

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Methods Mentioned

BETA
nuclear translocation
FRET
biosensors
transfection

Software Mentioned

Fiji
scipy
ImageJ

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