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Updated: May 15, 2026
10:17
A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
Published on: April 29, 2022
The serine/threonine phosphatase PPM1B (PP2Cβ) selectively modulates PPARγ activity
Ismayil Tasdelen1, Olivier van Beekum, Olena Gorbenko
1Department of Metabolic Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands.
The Biochemical Journal
|January 17, 2013
Summary
The protein phosphatase PPM1B dephosphorylates and selectively modulates the activity of the nuclear receptor PPARγ. This interaction occurs in the nucleus and affects PPARγ-mediated gene expression in adipocytes.
Area of Science:
- Molecular Biology
- Cellular Regulation
- Biochemistry
Background:
- Reversible protein phosphorylation regulates transcription factors like PPARγ.
- Phosphorylation at Ser(112) and Ser(273) alters PPARγ transcriptional activity.
- Few enzymes are known to dephosphorylate nuclear receptors.
Purpose of the Study:
- To identify novel proteins that regulate PPARγ.
- To investigate the role of identified proteins in PPARγ dephosphorylation and activity.
Main Methods:
- Immunoprecipitation assays.
- Tandem mass spectrometry (MS) analysis.
- Cellular knockdown experiments in 3T3-L1 adipocytes.
Main Results:
- Identified PPM1B (protein phosphatase, Mg(2+)/Mn(2+) dependent, 1B) as a PPARγ-interacting protein.
- Demonstrated PPM1B dephosphorylates PPARγ in vitro and in intact cells.
- Showed PPM1B enhances PPARγ-mediated transcription via Ser(112) dephosphorylation.
- Observed PPM1B knockdown selectively alters PPARγ target gene expression.
Conclusions:
- PPM1B is a novel nuclear phosphatase that interacts with PPARγ.
- PPM1B directly dephosphorylates PPARγ, enhancing its transcriptional activity.
- PPM1B acts as a selective modulator of PPARγ activity.
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