PMID- 18223677
OWN - NLM
STAT- MEDLINE
DCOM- 20080701
LR  - 20211203
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 27
IP  - 26
DP  - 2008 Jun 12
TI  - Post-translational regulation of the ERK phosphatase DUSP6/MKP3 by the mTOR 
      pathway.
PG  - 3685-91
LID - 10.1038/sj.onc.1211040 [doi]
AB  - MAP kinases phosphatases (MKPs) belong to the dual-specificity phosphatase family 
      (DUSP) and dephosphorylate phosphothreonine and phosphotyrosine within MAP 
      kinases. We had previously shown that DUSP6/MKP-3 was phosphorylated and degraded 
      upon growth factor stimulation, in a MEK-dependent manner. Here we show that 
      another pathway involved in growth factor signaling, the PI3K/mTOR signaling 
      pathway, accounts for a part of the phosphorylation and degradation of DUSP6 
      induced by serum growth factors, as evidenced by experiments using 
      pharmacological inhibitors of PI3 kinase and mammalian target of rapamycin 
      (mTOR). Moreover, specific agonists of the mTOR pathway, such as amino acids or 
      insulin/IGF-1, which do not activate extracellular signal regulated kinases 
      (ERKs) in our cellular model, were also able to induce the phosphorylation and 
      degradation of DUSP6. However, a basal activity of MEK was required for the mTOR 
      pathway-mediated phosphorylation to occur. Mutagenesis studies identified serine 
      159 within DUSP6 as the target of the mTOR pathway. The ERK phosphatase DUSP6 may 
      thus constitute a novel branch-point of the crosstalk between two major signaling 
      pathways induced by growth factors, the MEK/ERK pathway and the PI3K/mTOR 
      pathway.
FAU - Bermudez, O
AU  - Bermudez O
AD  - Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, 
      Centre Antoine Lacassagne, University of Nice-Sophia Antipolis, Nice, France.
FAU - Marchetti, S
AU  - Marchetti S
FAU - Pages, G
AU  - Pages G
FAU - Gimond, C
AU  - Gimond C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080128
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 6)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cricetinae
MH  - Dual Specificity Phosphatase 6/*metabolism
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Phosphorylation
MH  - Protein Kinases/*physiology
MH  - *Protein Processing, Post-Translational
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases
EDAT- 2008/01/29 09:00
MHDA- 2008/07/02 09:00
CRDT- 2008/01/29 09:00
PHST- 2008/01/29 09:00 [pubmed]
PHST- 2008/07/02 09:00 [medline]
PHST- 2008/01/29 09:00 [entrez]
AID - 1211040 [pii]
AID - 10.1038/sj.onc.1211040 [doi]
PST - ppublish
SO  - Oncogene. 2008 Jun 12;27(26):3685-91. doi: 10.1038/sj.onc.1211040. Epub 2008 Jan 
      28.