PMID- 22260695
OWN - NLM
STAT- MEDLINE
DCOM- 20120518
LR  - 20220414
IS  - 1470-8752 (Electronic)
IS  - 0300-5127 (Linking)
VI  - 40
IP  - 1
DP  - 2012 Feb
TI  - ERK phosphorylation and nuclear accumulation: insights from single-cell imaging.
PG  - 224-9
LID - 10.1042/BST20110662 [doi]
AB  - Many stimuli mediate activation and nuclear translocation of ERK 
      (extracellular-signal-regulated kinase) by phosphorylation on the TEY 
      (Thr-Glu-Tyr) motif. This is necessary to initiate transcriptional programmes 
      controlling cellular responses, but the mechanisms that govern ERK nuclear 
      targeting are unclear. Single-cell imaging approaches have done much to increase 
      our understanding of input-output relationships in the ERK cascade, but few 
      studies have addressed how the range of ERK phosphorylation responses observed in 
      cell populations influences subcellular localization. Using automated microscopy 
      to explore ERK regulation in single adherent cells, we find that nuclear 
      localization responses increase in proportion to stimulus level, but not the 
      level of TEY phosphorylation. This phosphorylation-unattributable nuclear 
      localization response occurs in the presence of tyrosine phosphatase and protein 
      synthesis inhibitors. It is also seen with a catalytically inactive ERK2-GFP 
      (green fluorescent protein) mutant, and with a mutant incapable of binding the 
      DEF (docking site for ERK, F/Y-X-F/Y-P) domains found in many ERK-binding 
      partners. It is, however, reduced by MEK (mitogen-activated protein kinase/ERK 
      kinase) inhibition and by mutations preventing TEY phosphorylation or in the ERK 
      common docking region. We therefore show that TEY phosphorylation of ERK is 
      necessary, but not sufficient, for the full nuclear accumulation response and 
      that this 'phosphorylation-unattributable' component of stimulus-mediated ERK 
      nuclear localization requires association with partner proteins via the common 
      docking motif.
FAU - Caunt, Christopher J
AU  - Caunt CJ
AD  - Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK. 
      c.caunt@bath.ac.uk
FAU - McArdle, Craig A
AU  - McArdle CA
LA  - eng
GR  - 078407/Wellcome Trust/United Kingdom
GR  - 084588/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Soc Trans
JT  - Biochemical Society transactions
JID - 7506897
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Amino Acid Motifs
MH  - Cell Nucleus/metabolism
MH  - Humans
MH  - Microscopy, Fluorescence
MH  - Mitogen-Activated Protein Kinase 1/chemistry/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/chemistry/*metabolism
MH  - Phosphorylation
MH  - Protein Transport
MH  - *Single-Cell Analysis
EDAT- 2012/01/21 06:00
MHDA- 2012/05/19 06:00
CRDT- 2012/01/21 06:00
PHST- 2012/01/21 06:00 [entrez]
PHST- 2012/01/21 06:00 [pubmed]
PHST- 2012/05/19 06:00 [medline]
AID - BST20110662 [pii]
AID - 10.1042/BST20110662 [doi]
PST - ppublish
SO  - Biochem Soc Trans. 2012 Feb;40(1):224-9. doi: 10.1042/BST20110662.