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Updated: Jun 7, 2025
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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
Published on: April 29, 2022
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PPP1R2 stimulates protein phosphatase-1 through stabilisation of dynamic subunit interactions
Sarah Lemaire1, Mónica Ferreira1, Zander Claes1
1Laboratory of Biosignaling & Therapeutics, KU Leuven Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium.
Nature Communications
|November 13, 2024
Summary
Protein phosphatase 1 (PP1) function is modulated by regulatory subunits. PPP1R2 (Inhibitor-2) stabilizes specific PP1 holoenzymes, like PP1:RepoMan, promoting substrate dephosphorylation and cellular signaling.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Protein Ser/Thr phosphatase PP1 functions with regulatory subunits (RIPPOs).
- PPP1R2 (Inhibitor-2) is an ancient RIPPO with debated roles in PP1 activity.
- The precise mechanism of PPP1R2's influence on PP1 in cells remains unclear.
Purpose of the Study:
- To elucidate how PPP1R2 affects Protein Ser/Thr phosphatase PP1 function in intact cells.
- To investigate the molecular mechanisms underlying PPP1R2-mediated modulation of PP1 holoenzymes.
Main Methods:
- Utilized specific research tools to study PP1:PPP1R2 interactions.
- Investigated the structural and functional consequences of PPP1R2 recruitment to PP1 holoenzymes.
- Analyzed the impact of PPP1R2 on PP1 holoenzyme stability and substrate dephosphorylation.
Main Results:
- PPP1R2 stabilizes specific PP1 holoenzymes, such as PP1:RepoMan.
- PPP1R2 disrupts an inhibitory interaction within PP1 and creates a new RepoMan-binding site.
- The stabilized PP1:RepoMan:PPP1R2 complex is resistant to disruption by other RIPPOs.
Conclusions:
- PPP1R2 acts as a stabilizer for a subset of PP1 holoenzymes, enhancing their phosphatase activity.
- PPP1R2 modulates PP1 function by altering holoenzyme composition and stability.
- This stabilization mechanism provides insights into the regulation of cellular signaling pathways dependent on PP1 activity.
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