PMID- 16601071
OWN - NLM
STAT- MEDLINE
DCOM- 20060928
LR  - 20211203
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 20
IP  - 8
DP  - 2006 Aug
TI  - The role of c-Jun N-terminal kinase, p38, and extracellular signal-regulated 
      kinase in insulin-induced Thr69 and Thr71 phosphorylation of activating 
      transcription factor 2.
PG  - 1786-95
AB  - The stimulation of cells with physiological concentrations of insulin induces a 
      variety of responses, e.g. an increase in glucose uptake, induction of glycogen 
      and protein synthesis, and gene expression. One of the determinants regulating 
      insulin-mediated gene expression may be activating transcription factor 2 (ATF2). 
      Insulin activates ATF2 by phosphorylation of Thr69 and Thr71 via a two-step 
      mechanism, in which ATF2-Thr71 phosphorylation precedes the induction of 
      ATF2-Thr69+71 phosphorylation by several minutes. We previously found that in 
      c-Jun N-terminal kinase (JNK)-/- fibroblasts, cooperation of the ERK1/2 and p38 
      pathways is required for two-step ATF2-Thr69+71 phosphorylation in response to 
      growth factors. Because JNK is also capable of phosphorylating ATF2, we assessed 
      the involvement of JNK, ERK1/2 and p38 in the insulin-induced two-step ATF2 
      phosphorylation in JNK-expressing A14 fibroblasts and 3T3L1-adipocytes. The 
      induction of ATF2-Thr71 phosphorylation was sensitive to MAPK kinase (MEK) 
      1/2-inhibition with U0126, and this phosphorylation coincided with nuclear 
      translocation of phosphorylated ERK1/2. Use of the JNK inhibitor SP600125 or 
      expression of dominant-negative JNK-activator SAPK kinase (SEK1) prevented the 
      induction of ATF2-Thr69+71, but not ATF2-Thr71 phosphorylation by insulin. 
      ATF2-dependent transcription was also sensitive to SP-treatment. Abrogation of 
      p38 activation with SB203580 or expression of dominant-negative MKK6 had no 
      inhibitory effect on these events. In agreement with this, the onset of 
      ATF2-Thr69+71 phosphorylation coincided with the nuclear translocation of 
      phosphorylated JNK. Finally, in vitro kinase assays using nuclear extracts 
      indicated that ERK1/2 preceded JNK translocation. We conclude that sequential 
      activation and nuclear appearance of ERK1/2 and JNK, rather than p38, underlies 
      the two-step insulin-induced ATF2 phosphorylation in JNK-expressing cells.
FAU - Baan, Bart
AU  - Baan B
AD  - Department of Molecular Cell Biology, Section Signal Transduction and Ageing, 
      Leiden University Medical Centre, The Netherlands.
FAU - van Dam, Hans
AU  - van Dam H
FAU - van der Zon, Gerard C M
AU  - van der Zon GC
FAU - Maassen, J Antonie
AU  - Maassen JA
FAU - Ouwens, D Margriet
AU  - Ouwens DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060406
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Atf2 protein, mouse)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Activating Transcription Factor 2/*metabolism
MH  - Active Transport, Cell Nucleus
MH  - Animals
MH  - Enzyme Inhibitors/pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/*physiology
MH  - Humans
MH  - Insulin/*pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/*physiology
MH  - Mice
MH  - Models, Biological
MH  - NIH 3T3 Cells
MH  - Phosphorylation/*drug effects
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein Transport
MH  - Time Factors
MH  - Transfection
MH  - p38 Mitogen-Activated Protein Kinases/*physiology
EDAT- 2006/04/08 09:00
MHDA- 2006/09/29 09:00
CRDT- 2006/04/08 09:00
PHST- 2006/04/08 09:00 [pubmed]
PHST- 2006/09/29 09:00 [medline]
PHST- 2006/04/08 09:00 [entrez]
AID - me.2005-0289 [pii]
AID - 10.1210/me.2005-0289 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2006 Aug;20(8):1786-95. doi: 10.1210/me.2005-0289. Epub 2006 Apr 
      6.