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A kinetic model of ERK cyclic pathway on substrate control
1Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. tsuyoshi.hirashima@gmail.com
Mathematical Biosciences
|June 19, 2012
Summary
Downstream substrates can control extracellular signal-regulated kinase (ERK) activity by directly interacting with it. This interaction modulates ERK phosphorylation and can lead to nuclear accumulation, revealing a novel mechanism for substrate-mediated signaling.
Area of Science:
- Cellular signaling pathways
- Molecular dynamics and kinetics
Background:
- Extracellular signal-regulated kinase (ERK) is central to phosphorylation-dephosphorylation signaling cascades.
- ERK's phosphorylation and localization are influenced by downstream substrates, but the precise mechanism remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which downstream substrates modulate ERK signaling properties.
- To investigate substrate-mediated control of ERK phosphorylation levels and spatial distribution.
Main Methods:
- Development of a mass-action kinetic model for the ERK signaling cycle.
- Inclusion of direct ERK-substrate interactions within the kinetic model.
- Analysis of model behavior considering cytosolic and nuclear cellular compartments.
Main Results:
- The model demonstrates that substrates can directly interact with ERK to modulate its activity.
- Substrate addition can result in positive or negative control of ERK phosphorylation, dependent on kinetic parameters.
- Substrates can promote nuclear accumulation of ERK, acting as a nuclear anchor.
Conclusions:
- Direct substrate interaction provides a mechanistic explanation for substrate-mediated modulation of ERK signaling.
- Substrates play a critical role in regulating both the activity and localization of ERK within the cell.
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