phosphorylation cascade
Definition
A phosphorylation cascade is a sequential series of protein phosphorylation events where one activated kinase phosphorylates and activates the next kinase in the pathway, amplifying and transmitting cellular signals. Each step involves the transfer of a phosphate group from ATP to specific amino acid residues (typically serine, threonine, or tyrosine) on target proteins, causing conformational changes that modulate their activity. This mechanism enables cells to rapidly amplify weak extracellular signals, integrate multiple inputs, and generate diverse cellular responses. Phosphorylation cascades are fundamental to signal transduction pathways including MAPK/ERK, PI3K/AKT, and JAK/STAT pathways, regulating critical processes such as cell growth, differentiation, apoptosis, and immune responses. Dysregulation of these cascades is implicated in cancer, diabetes, and inflammatory diseases.
Visualize phosphorylation cascade in Nodes Bio
Researchers can map phosphorylation cascades as directed network graphs where nodes represent kinases and substrates, and edges indicate phosphorylation events. Nodes Bio enables visualization of cascade hierarchy, identification of key regulatory nodes, and analysis of pathway crosstalk. Users can overlay experimental phosphoproteomics data to identify activated cascade branches under different conditions, trace signal propagation from receptors to transcription factors, and predict downstream effects of kinase inhibitors.
Visualization Ideas:
- Hierarchical directed graphs showing kinase-substrate relationships from receptor to transcription factor
- Time-series networks displaying temporal activation of cascade components following ligand stimulation
- Multi-layer networks comparing phosphorylation cascade activation across different cell types or disease states
Example Use Case
A cancer researcher investigating resistance to EGFR inhibitors uses phosphoproteomics to profile signaling changes in resistant cell lines. By mapping the data in Nodes Bio, they discover hyperactivation of an alternative phosphorylation cascade through MET receptor, bypassing EGFR blockade. The network visualization reveals that MET activation triggers the PI3K/AKT/mTOR cascade, maintaining cell survival despite EGFR inhibition. This insight guides combination therapy development targeting both EGFR and MET pathways to overcome resistance.