TGFsignalen

TGFsignalen, or Transforming Growth Factor signaling, describes a conserved set of pathways by which TGF-β family ligands regulate cellular activities. The family includes TGF-β1–3, activins, nodal, and related bone morphogenetic proteins, which bind to type II serine/threonine kinase receptors, recruiting and phosphorylating type I receptors. In the canonical pathway, activated type I receptors phosphorylate receptor-regulated SMADs (SMAD2 and SMAD3), which form a complex with SMAD4 and translocate to the nucleus to regulate target genes involved in cell cycle control, differentiation, extracellular matrix production, and immune responses. Non-SMAD pathways, such as MAP kinases, PI3K/AKT, and Rho-like GTPases, can also be activated, contributing to diverse outcomes.

Signaling is tightly regulated at multiple levels. TGF-β ligands are often secreted as latent complexes with latency-associated peptide (LAP) and latent TGF-β binding protein (LTBP); activation can occur through proteases, integrins, or mechanical forces. Receptor abundance, intracellular SMAD availability, and crosstalk with other signaling networks influence the cellular response. Distinct receptor compositions and ligand contexts can yield pro-proliferative, anti-proliferative, profibrotic, or immunomodulatory effects.

Physiological roles of TGF-signalen are broad, including regulation of development, tissue homeostasis, wound healing, and immune function. In adults, signaling maintains extracellular matrix balance and can suppress excessive proliferation; however, in cancer and fibrosis, the pathway may promote invasion, immune evasion, or fibrotic remodeling, depending on context.

Therapeutic approaches aim to modulate TGF-β signaling in diseases such as fibrosis, cancer, and vascular disorders, using ligand traps, neutralizing antibodies, or receptor kinase inhibitors. Ongoing research seeks to clarify context-specific effects and improve therapeutic strategies.