PMID- 16816403
OWN - NLM
STAT- MEDLINE
DCOM- 20061031
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 37
DP  - 2006 Sep 15
TI  - AKT-independent phosphorylation of TSC2 and activation of mTOR and ribosomal 
      protein S6 kinase signaling by prostaglandin F2alpha.
PG  - 26904-13
AB  - Prostaglandin F2alpha (PGF2alpha) is an important mediator of corpus luteum (CL) 
      regression, although the cellular signaling events that mediate this process have 
      not been clearly identified. It is established that PGF2alpha binds to a 
      G-proteincoupled receptor (GPCR) to stimulate protein kinase C (PKC) and 
      Raf-MEK-Erk signaling in luteal cells. The present experiments were performed to 
      determine whether PGF2alpha stimulates the mammalian target of rapamycin 
      (mTOR)/ribosomal protein S6 kinase 1 (S6K1) signaling pathway in steroidogenic 
      luteal cells. We demonstrate that PGF2alpha treatment results in a timeand 
      concentration-dependent stimulation of the phosphorylation and activation of 
      S6K1. The stimulation of S6K1 in response to PGF2alpha treatment was abolished by 
      the mTOR inhibitor rapamycin. Treatment with PGF2alpha did not increase AKT 
      phosphorylation but increased the phosphorylation of Erk and the tumor suppressor 
      protein tuberous sclerosis complex 2 (TSC2), an upstream regulator of mTOR. The 
      effects of PGF2alpha were mimicked by the PKC activator PMA and inhibited by 
      U0126, a MEK1 inhibitor. The activation of mTOR/S6K1 and putative down stream 
      processes involving the translational apparatus (i.e. 4EBP1 phosphorylation, 
      release of 4EBP1 binding in m(7)G cap binding assays, and the phosphorylation and 
      synthesis of S6) were completely sensitive to treatment with rapamycin, 
      implicating mTOR in the actions of PGF2alpha. Taken together, our data suggest 
      that GPCR activation in response to PGF2alpha stimulates the mTOR pathway which 
      increases the translational machinery in luteal cells. The translation of 
      proteins under the control of mTOR may have implications for luteal development 
      and regression and offer new strategies for therapeutic intervention in 
      PGF2alpha-target tissues.
FAU - Arvisais, Edward W
AU  - Arvisais EW
AD  - Olson Center for Women's Health, Department of Obstetrics and Gynecology, 
      University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA.
FAU - Romanelli, Angela
AU  - Romanelli A
FAU - Hou, Xiaoying
AU  - Hou X
FAU - Davis, John S
AU  - Davis JS
LA  - eng
GR  - R01HD38813/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060701
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - B7IN85G1HY (Dinoprost)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Dinoprost/*metabolism
MH  - Female
MH  - Luteal Cells/metabolism
MH  - Ovary/metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*chemistry
MH  - Ribosomal Protein S6 Kinases/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/chemistry/*metabolism
EDAT- 2006/07/04 09:00
MHDA- 2006/11/01 09:00
CRDT- 2006/07/04 09:00
PHST- 2006/07/04 09:00 [pubmed]
PHST- 2006/11/01 09:00 [medline]
PHST- 2006/07/04 09:00 [entrez]
AID - S0021-9258(19)34867-7 [pii]
AID - 10.1074/jbc.M605371200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Sep 15;281(37):26904-13. doi: 10.1074/jbc.M605371200. Epub 2006 
      Jul 1.