PI3K/Akt
Definition
The PI3K/Akt signaling pathway is a critical intracellular cascade that regulates cell survival, growth, proliferation, metabolism, and angiogenesis. Phosphoinositide 3-kinase (PI3K) phosphorylates membrane lipids to generate PIP3, which recruits Akt (also called PKB) to the plasma membrane where it becomes activated through phosphorylation. Once activated, Akt phosphorylates numerous downstream substrates including mTOR, GSK3β, and FOXO transcription factors, influencing diverse cellular processes. This pathway is frequently dysregulated in cancer, diabetes, and neurological disorders, making it a major therapeutic target. The pathway is negatively regulated by PTEN phosphatase, and mutations affecting PI3K/Akt components are among the most common oncogenic alterations.
Visualize PI3K/Akt in Nodes Bio
Researchers can map PI3K/Akt pathway components and their interactions to identify dysregulated nodes in disease contexts. Network visualization reveals crosstalk with other signaling cascades like MAPK/ERK and mTOR pathways, highlights feedback loops, and shows how pathway perturbations propagate through cellular networks. This enables identification of optimal therapeutic intervention points and prediction of drug resistance mechanisms.
Visualization Ideas:
- Protein-protein interaction network showing PI3K/Akt pathway components and downstream effectors
- Multi-layer network integrating PI3K/Akt with parallel MAPK and mTOR signaling cascades
- Phosphorylation cascade network mapping temporal activation dynamics from receptor to nuclear targets
Example Use Case
An oncology research team investigating resistance to PI3K inhibitors in breast cancer uses network analysis to map the complete PI3K/Akt signaling network in resistant cell lines. By integrating phosphoproteomics data, they visualize compensatory pathway activation through receptor tyrosine kinases and identify unexpected crosstalk with Wnt/β-catenin signaling. The network reveals that GSK3β inhibition by hyperactive Akt stabilizes β-catenin, suggesting combination therapy targeting both pathways could overcome resistance.