| 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
|
|
WOS Category
|
CELL BIOLOGY
|
| Resource |
| 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) |
