JAK-STAT pathway
Definition
The JAK-STAT pathway is a rapid membrane-to-nucleus signaling cascade that transduces extracellular signals from cytokines and growth factors into gene expression changes. When cytokines bind to cell surface receptors, they activate Janus kinases (JAKs), which phosphorylate Signal Transducers and Activators of Transcription (STATs). Phosphorylated STATs dimerize, translocate to the nucleus, and regulate transcription of target genes involved in immunity, cell proliferation, differentiation, and apoptosis. This pathway is critical for immune responses, hematopoiesis, and inflammation. Dysregulation of JAK-STAT signaling is implicated in autoimmune diseases, myeloproliferative disorders, and various cancers, making it a major therapeutic target for JAK inhibitors like tofacitinib and ruxolitinib.
Visualize JAK-STAT pathway in Nodes Bio
Researchers can map JAK-STAT pathway components as interconnected nodes showing cytokine receptors, JAK proteins, STAT family members, and downstream target genes. Network visualization reveals crosstalk with other pathways, identifies feedback loops and negative regulators like SOCS proteins, and highlights disease-associated mutations. Causal inference tools can predict how JAK inhibitors affect downstream gene expression patterns across different cellular contexts.
Visualization Ideas:
- Cytokine-receptor-JAK-STAT signaling cascade with phosphorylation events
- STAT target gene regulatory networks across different cell types
- JAK inhibitor mechanism of action showing blocked interactions and downstream effects
Example Use Case
An immunology research team investigating rheumatoid arthritis uses Nodes Bio to map how IL-6 activates the JAK1/STAT3 axis in synovial fibroblasts. They visualize the pathway network including upstream cytokine signals, JAK-STAT components, and downstream inflammatory mediators like MMP genes. By integrating patient RNA-seq data, they identify aberrant STAT3 activation patterns and model how selective JAK1 inhibitors could normalize the inflammatory network. The visualization reveals unexpected crosstalk with NF-κB signaling, suggesting combination therapy opportunities.