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Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
MAPK Signaling Cascades01:07

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Calmodulin-dependent Signaling01:16

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Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
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Updated: Jul 13, 2026

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors.

Birgit Schoeberl1, Claudia Eichler-Jonsson, Ernst Dieter Gilles

  • 1Max Planck Institute for Dynamics of Complex Technical Systems, Leipziger Str. 44, D-39120 Magdeburg, Germany.

Nature Biotechnology
|March 30, 2002
PubMed
Summary
This summary is machine-generated.

This study introduces a computational model for epidermal growth factor (EGF) signaling pathways. The model reveals that initial receptor activation speed, not ligand concentration, dictates cellular response stability.

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Area of Science:

  • Computational biology
  • Cell signaling
  • Systems biology

Background:

  • Epidermal growth factor (EGF) receptor pathways are crucial for cellular processes.
  • Understanding the quantitative dynamics of these pathways is complex.
  • Existing models may not fully capture the integrated nature of signal transduction.

Purpose of the Study:

  • To develop a computational model for intracellular signal networks.
  • To represent epidermal growth factor (EGF) receptor signal pathways quantitatively, dynamically, and topologically.
  • To investigate signal-response relationships from EGF binding to downstream protein activation.

Main Methods:

  • Development of an integrated computational model.
  • Simulation of EGF receptor signal pathways.
  • Quantitative analysis of signal dynamics and network topology.
  • Comparison of model predictions with experimental data.

Main Results:

  • The model provides insights into EGF-induced signal-response relationships.
  • EGF responses demonstrate stability across a 100-fold range of ligand concentration.
  • Initial velocity of receptor activation is identified as the critical parameter for signal efficacy.
  • Model predictions align with experimental findings on ERK-1/2 phosphorylation and c-fos expression.

Conclusions:

  • The computational model accurately represents EGF signaling dynamics.
  • Signal response stability is primarily determined by the rate of receptor activation.
  • The model serves as a valuable tool for understanding complex cell signaling networks.