TGFroutes

TGFroutes is a term used in biology to describe curated maps of signaling pathways initiated by members of the Transforming Growth Factor (TGF) family. The concept covers both the canonical TGF-β signaling through SMAD proteins and the array of non-SMAD signaling branches that intersect with other cellular pathways, reflecting the diverse roles of TGF family ligands in development, homeostasis, and disease.

Structure and content. TGFroutes are typically represented as directed graphs in which nodes denote ligands, receptors, intracellular mediators, and transcriptional regulators, while edges indicate binding events, activation, or repression. Metadata accompanying each route includes tissue or cell type, species, ligand concentration, duration of signaling, and experimental context. The scope often spans major ligands such as TGF-β isoforms, activins, BMPs, and GDFs, their type I and II receptors, and downstream effectors including SMAD2/3/4 and SMAD-independent mediators like MAPKs, PI3K/AKT, and Rho-family GTPases. Cross-talk with pathways such as WNT, Notch, and NF-κB is commonly documented.

Applications and use. TGFroutes serve as resources for pathway analysis, systems biology modeling, and interpretation of omics data. They aid in identifying potential drug targets, understanding context-dependent responses (e.g., fibrosis, cancer, immune regulation), and comparing signaling architecture across species or tissues.

Curation and limitations. Content is typically compiled from peer-reviewed literature, public pathway databases, and high-throughput datasets, with ongoing updates and quality assessments. Limitations reflect the context-dependent nature of TGF signaling, incomplete knowledge of interactions, and variability between experimental systems.

See also. Transforming growth factor beta signaling; SMAD proteins; signaling pathway databases; systems biology.