The mitogen-activated protein kinase network, wired to dynamically function at multiple scales

Paolo Armando Gagliardi1, Olivier Pertz1

  • 1Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland.

Insights

The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway exhibits dynamic behaviors like pulsing and oscillations. Understanding these complex signaling dynamics across multiple scales is crucial for cell fate decisions.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Systems Biology

Background:

  • The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway is a critical signaling network.
  • It regulates fundamental cellular processes including cell cycle, survival, and differentiation.
  • Traditional biochemical methods have limitations in capturing pathway dynamics.

Purpose of the Study:

  • To explore the dynamic behaviors of the ERK signaling network.
  • To understand how receptor tyrosine kinases (RTKs) influence ERK dynamics through feedback mechanisms.
  • To investigate the role of ERK dynamics in cell fate decisions at both single-cell and collective levels.

Main Methods:

  • Utilizing advanced fluorescent biosensors to visualize ERK activity in real-time.
  • Employing biochemical assays to analyze feedback mechanisms within the MAPK network.
  • Observing and analyzing collective ERK wave behaviors in cellular systems.

Main Results:

  • Fluorescent biosensors revealed dynamic ERK behaviors like pulsing, oscillations, and amplitude modulation.
  • Specific feedback mechanisms from different RTKs encode distinct ERK dynamics.
  • Collective ERK wave behaviors were observed to coordinate cytoskeletal dynamics and cell fate decisions.

Conclusions:

  • The ERK signaling network exhibits complex, dynamic behaviors essential for cellular functions.
  • Understanding these dynamics requires multi-scale analysis, from molecular interactions to collective cell behaviors.
  • ERK dynamics play a key role in actuating cellular fates through cytoskeletal and transcriptional regulation.

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