phosphoproteome
Definition
The phosphoproteome encompasses all phosphorylated proteins within a cell, tissue, or organism at a given time, representing a dynamic snapshot of cellular signaling activity. Phosphorylation, the addition of phosphate groups to serine, threonine, or tyrosine residues, is a critical post-translational modification that regulates protein function, localization, and interactions. Studying the phosphoproteome reveals active signaling pathways, kinase-substrate relationships, and cellular responses to stimuli. This analysis is essential for understanding disease mechanisms, particularly in cancer where aberrant phosphorylation drives oncogenic signaling, and for identifying therapeutic targets. Phosphoproteomic profiling typically employs mass spectrometry combined with phosphopeptide enrichment techniques to identify and quantify thousands of phosphorylation sites across the proteome, providing insights into temporal signaling dynamics and pathway crosstalk.
Visualize phosphoproteome in Nodes Bio
Researchers can visualize phosphoproteomic data as dynamic signaling networks in Nodes Bio, mapping kinase-substrate relationships and phosphorylation cascades. By integrating phosphorylation site data with protein-protein interactions, users can identify activated pathways, discover novel regulatory nodes, and trace signal transduction from receptors to transcription factors. Network analysis reveals phosphorylation-dependent protein complexes and signaling hubs critical for cellular responses.
Visualization Ideas:
- Kinase-substrate interaction networks showing phosphorylation cascades
- Temporal phosphorylation dynamics networks comparing treatment timepoints
- Pathway enrichment maps highlighting differentially phosphorylated signaling modules
Example Use Case
A cancer research team investigates drug resistance in melanoma by comparing phosphoproteomes of sensitive versus resistant cell lines treated with a BRAF inhibitor. Mass spectrometry identifies 5,000 phosphorylation sites with altered abundance. By mapping these phosphosites onto signaling networks, researchers discover hyperphosphorylation of MEK and ERK pathway components in resistant cells, along with compensatory activation of PI3K/AKT signaling. This network view reveals bypass mechanisms and suggests rational combination therapies targeting both pathways to overcome resistance.