RRC ID 38210
Author Shindo Y, Iwamoto K, Mouri K, Hibino K, Tomita M, Kosako H, Sako Y, Takahashi K.
Title Conversion of graded phosphorylation into switch-like nuclear translocation via autoregulatory mechanisms in ERK signalling.
Journal Nat Commun
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.
Volume 7
Pages 10485
Published 2016-1-20
DOI 10.1038/ncomms10485
PII ncomms10485
PMID 26786866
PMC PMC4736105
MeSH Animals Cell Nucleus / metabolism* Extracellular Signal-Regulated MAP Kinases / genetics Extracellular Signal-Regulated MAP Kinases / metabolism* Mitogen-Activated Protein Kinase 1 / genetics Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / genetics Mitogen-Activated Protein Kinase 3 / metabolism PC12 Cells Phosphorylation / genetics Phosphorylation / physiology Protein Transport / genetics Protein Transport / physiology RNA Interference Rats
IF 12.121
Times Cited 28
DNA material pGEX-GFP-ERK2-His (RDB14152) pCMV-GFP-ERK2 (RDB14156) pACYC184-Venus-MEK1 (S218/222E delta32-51) (RDB14154).
Human and Animal Cells PC-12(RCB0009)