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Updated: Jun 9, 2026

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
Published on: October 4, 2024
Oscillatory dynamics of the extracellular signal-regulated kinase pathway
Harish Shankaran1, H Steven Wiley
1Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, WA 99352, USA.
Abstract:
The extracellular signal-regulated kinase (ERK) pathway is a central signaling pathway in development and disease and is regulated by multiple negative and positive feedback loops. Recent studies have shown negative feedback from ERK to upstream regulators can give rise to biochemical oscillations with a periodicity of between 15 and 30min. Feedback due to the stimulated transcription of negative regulators of the ERK pathway can also give rise to transcriptional oscillations with a periodicity of one to two hours. The biological significance of these oscillations is not clear, but recent evidence suggests that transcriptional oscillations participate in developmental processes, such as somite formation. Biochemical oscillations are more enigmatic, but could provide a mechanism for encoding different types of inputs into a common signaling pathway.
Insights
The extracellular signal-regulated kinase (ERK) pathway exhibits oscillations due to feedback loops. These oscillations, both biochemical and transcriptional, may play roles in development and signaling.
Area of Science:
- Molecular Biology
- Cell Signaling
- Developmental Biology
Background:
- The extracellular signal-regulated kinase (ERK) pathway is crucial in cellular processes, development, and disease.
- This pathway is intricately regulated by complex positive and negative feedback mechanisms.
Purpose of the Study:
- To investigate the nature and potential significance of oscillations generated by feedback loops within the ERK pathway.
- To explore the distinct characteristics and biological roles of biochemical versus transcriptional oscillations.
Main Methods:
- Analysis of existing studies on ERK pathway feedback mechanisms.
- Characterization of oscillation periodicity (15-30 min for biochemical, 1-2 hours for transcriptional).
Main Results:
- Negative feedback from ERK to upstream regulators generates biochemical oscillations.
- Stimulated transcription of ERK pathway negative regulators leads to transcriptional oscillations.
- Transcriptional oscillations are implicated in developmental processes like somite formation.
Conclusions:
- ERK pathway feedback loops generate distinct biochemical and transcriptional oscillations.
- The biological significance of these oscillations, particularly biochemical ones, requires further elucidation.
- Oscillations may serve as a mechanism for encoding diverse inputs within the ERK signaling network.
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