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Updated: Jul 13, 2026
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Oligopeptide Competition Assay for Phosphorylation Site Determination
Published on: May 18, 2017
MAPK kinases as nucleo-cytoplasmic shuttles for PPARgamma
Elke Burgermeister1, Rony Seger
1Department of Medicine II, Klinikum rechts der Isar, Technical University, Munich, Germany.
Cell Cycle (Georgetown, Tex.)
|July 6, 2007
Summary
Mitogenic stimulation suppresses Peroxisome proliferator-activated receptor-gamma (PPARgamma) activity via the ERK/MAPK pathway, causing its nuclear export. This mechanism may control PPARgamma
Area of Science:
- Molecular Biology
- Cell Signaling
- Nuclear Receptor Research
Background:
- Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor regulating differentiation, metabolism, and immunity.
- PPARgamma ligands are used for type 2 diabetes and show promise for inflammation and cancer treatment.
- Mitogenic stimulation typically suppresses PPARgamma's genomic activity.
Purpose of the Study:
- To elucidate the mechanism by which mitogenic stimulation downregulates PPARgamma activity.
- To investigate the role of the ERK/MAPK signaling cascade in PPARgamma regulation.
- To explore the implications of PPARgamma subcellular localization for its genomic and nongenomic functions.
Main Methods:
- Analysis of the extracellular signal-regulated kinase 1/2 (ERK/MAPK) signaling pathway.
- Investigation of PPARgamma phosphorylation and nucleo-cytoplasmic shuttling.
- Study of the interaction between MEK and PPARgamma.
Main Results:
- Mitogenic stimulation downregulates PPARgamma activity primarily through the ERK/MAPK pathway.
- This downregulation involves inhibitory phosphorylation and modulation of PPARgamma's subcellular localization.
- MEK-mediated nuclear export of PPARgamma, accompanied by its cytoplasmic activities, is a key regulatory mechanism.
- The MEK-dependent shuttle may control both nuclear and extra-nuclear PPARgamma actions.
Conclusions:
- The ERK/MAPK pathway, particularly MEK-dependent nuclear export, is crucial for regulating PPARgamma activity.
- Subcellular localization changes of PPARgamma offer potential therapeutic targets for inflammatory and proliferation-related diseases.
- This mechanism may also regulate the activity of other nuclear receptors.
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