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Updated: Jun 10, 2026
Oligopeptide Competition Assay for Phosphorylation Site Determination
Published on: May 18, 2017
Phosphorylation control of nuclear receptors
Sébastien Lalevée1, Christine Ferry, Cécile Rochette-Egly
1Department of Functional Denomics, Institut de Genetique et de Biologie Molecularie et Cellulaire, Strasbourg, France.
Abstract:
Most transcription factors including nuclear receptors (NRs) act as sensors of the extracellular and intracellular compartments. As such, NRs serve as integrating platforms for a variety of stimuli and are targets for Post-translational modifications such as phosphorylations. During the last decade, knowledge of NRs phosphorylation advanced considerably because of the emergence of new technologies. Indeed, the development of a wide range of phosphorylation site databases, high accuracy mass spectrometry, and phospho-specific antibodies allowed the identification of multiple novel phosphorylation sites in NRs. New and improved methods also emerge to connect these data with the downstream consequences of phosphorylation on NRs structure (computational prediction, NMR), intracellular localization (FRAP), interaction with coregulators (proteomics, FRET, FLIM), and affinity for DNA (ChIP, ChIP-seq, FRAP). In the future, such integrated strategies should provide data with a treasure-trove of information about the integration of numerous signaling events by NRs.
Insights
Nuclear receptors (NRs) integrate cellular signals through phosphorylation. Advanced technologies now reveal how these modifications impact NR function, structure, and interactions, offering new insights into cellular signaling.
Area of Science:
- Molecular Biology
- Cellular Signaling
- Biochemistry
Background:
- Transcription factors, including nuclear receptors (NRs), function as cellular sensors.
- NRs integrate extracellular and intracellular stimuli and are regulated by post-translational modifications like phosphorylation.
Purpose of the Study:
- To review advancements in understanding NR phosphorylation.
- To highlight how new technologies facilitate the study of NR phosphorylation and its functional consequences.
Main Methods:
- Development of phosphorylation site databases.
- High-accuracy mass spectrometry for site identification.
- Phospho-specific antibodies for NR analysis.
- Computational prediction, NMR, FRAP, proteomics, FRET, FLIM, ChIP, and ChIP-seq for functional analysis.
Main Results:
- Numerous novel phosphorylation sites in NRs have been identified.
- New methods link phosphorylation to NR structure, localization, coregulator interactions, and DNA binding.
- Significant progress has been made in understanding NR phosphorylation over the last decade.
Conclusions:
- Integrated strategies using advanced technologies provide comprehensive data on NR signaling integration.
- Future research will further elucidate the role of phosphorylation in integrating diverse signaling events by NRs.
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