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MAPK Signaling Cascades

MAPK Signaling Cascades

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...

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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...

Assembly of Signaling Complexes

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The Ras Gene

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Related Experiment Video

Updated: Nov 9, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

Reusability and composability in process description maps: RAS-RAF-MEK-ERK signalling.

Alexander Mazein^1,2, Adrien Rougny^3,4, Jonathan R Karr^5,6

¹Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg.

Briefings in Bioinformatics

|April 9, 2021

Summary

Creating modular and composable molecular network maps is crucial for disease modeling. This study identifies design principles and challenges for reusable network components to facilitate collaborative research in cancer signaling.

Keywords:

compatibility composability modularity process description quality verification reusability systems biology

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Area of Science:

Systems biology
Computational biology
Molecular network analysis

Background:

Detailed molecular maps are essential for understanding disease mechanisms and building predictive models.
Modularity and composability are key network features for large-scale collaborative research efforts.
Effective management of complex biological systems relies on composing multiple subsystems.

Purpose of the Study:

To examine the reusability and composability of manually built network components for assembling new disease models.
To identify design principles for managing complex biological systems to enhance sharing and reuse of network components.
To highlight challenges in creating composable network components for disease modeling.

Main Methods:

Manual review of the RAS-RAF-MEK-ERK cascade from Atlas of Cancer Signalling Network, PANTHER, and Reactome databases.
Assessment of network components for reusability and composability.
Identification of design principles and challenges for system management.

Main Results:

Manually built network components from different databases exhibit varying degrees of reusability and composability.
Key challenges include incompatible levels of detail and ambiguous representation of molecular complexes.
Design principles for managing complex systems can facilitate sharing and reuse of network components.

Conclusions:

Composable network components are vital for harnessing collaborative efforts in building comprehensive molecular maps of disease.
Addressing challenges in standardization and representation is necessary for effective assembly of disease models.
Developing clear design principles will improve the sharing and reuse of network components in systems biology research.