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Updated: Aug 15, 2026

Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco Transient Expression System
08:54

Imaging Spatial Reorganization of a MAPK Signaling Pathway Using the Tobacco Transient Expression System

Published on: March 20, 2016

Control of MAPK signalling: from complexity to what really matters

Jorrit J Hornberg1, Bernd Binder, Frank J Bruggeman

  • 1Department of Molecular Cell Physiology, Institute of Molecular Cell Biology, Faculty of Earth and Life Sciences, Vrije Universiteit, Amsterdam, The Netherlands.

Oncogene
|July 12, 2005
PubMed

Insights

This study reveals that specific reactions, particularly Raf activity, significantly control the epidermal growth factor signaling pathway

Area of Science:

  • Systems Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Oncogenesis arises from altered protein kinetics or abundance in cell signaling networks.
  • Signaling control is often distributed across multiple components, not confined to a single gene.
  • Identifying key reactions is crucial for understanding oncogene function.

Purpose of the Study:

  • To develop and apply a novel method for analyzing control in complex signaling networks.
  • To identify critical reactions governing the epidermal growth factor (EGF)-induced mitogen-activated protein kinase (MAPK) pathway.
  • To understand why certain genes, like Raf, function as oncogenes.

Main Methods:

  • Implementation of control analysis on a detailed kinetic model of the EGF-induced MAPK network.
  • Quantification of reaction control over ERK phosphorylation amplitude, duration, and integrated output.
  • Assessment of distributed control within the signaling network.

Main Results:

  • Control is distributed but non-random, with a few reactions dominating signaling.
  • Raf activity critically controls all characteristics of extracellular signal-regulated kinase (ERK) phosphorylation.
  • Reactions important for one signaling output characteristic are often important for others.

Conclusions:

  • The distributed control of signaling networks can be quantitatively assessed.
  • Raf's central role in controlling ERK phosphorylation dynamics explains its oncogenic potential.
  • The method predicts the impact of mutations and gene expression changes on signaling pathways.

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