MAPK cascade
Definition
The MAPK (Mitogen-Activated Protein Kinase) cascade is a highly conserved three-tiered phosphorylation signaling pathway that transduces extracellular signals from cell surface receptors to nuclear transcription factors. The cascade consists of sequential activation of three kinase families: MAP3K (MAPKKK), MAP2K (MAPKK), and MAPK. Upon receptor activation, MAP3Ks phosphorylate and activate MAP2Ks, which in turn phosphorylate MAPKs. Activated MAPKs then phosphorylate numerous cytoplasmic and nuclear substrates, regulating critical cellular processes including proliferation, differentiation, apoptosis, and stress responses. Major MAPK pathways include ERK1/2, JNK, p38, and ERK5, each responding to distinct stimuli and controlling specific biological outcomes. This amplification mechanism allows cells to convert graded extracellular signals into decisive cellular responses.
Visualize MAPK cascade in Nodes Bio
Researchers can map MAPK cascade components as hierarchical network layers, visualizing phosphorylation dependencies and signal flow from receptors to transcription factors. Nodes Bio enables identification of pathway crosstalk points, feedback loops, and scaffold protein interactions. Users can overlay expression data or mutation status to identify dysregulated nodes in disease contexts, and trace how perturbations propagate through the cascade to predict downstream effects on gene expression programs.
Visualization Ideas:
- Hierarchical three-layer network showing MAP3K→MAP2K→MAPK phosphorylation flow with temporal activation dynamics
- Multi-pathway comparison network displaying ERK, JNK, p38, and ERK5 cascades with shared upstream activators and distinct downstream targets
- Disease-specific MAPK network overlaying mutation hotspots and drug target nodes in cancer signaling pathways
Example Use Case
A cancer researcher investigating resistance to BRAF inhibitors in melanoma uses network visualization to map the ERK MAPK cascade. By integrating phosphoproteomics data from drug-resistant cell lines, they identify unexpected activation of alternative MAP3Ks (like CRAF and MAP3K8) that bypass BRAF inhibition. The network reveals feedback reactivation of MEK1/2 and compensatory signaling through parallel p38 MAPK pathways. This visualization guides combination therapy strategies targeting multiple cascade nodes simultaneously to overcome resistance mechanisms.