Transforming Growth Factor Beta Receptor-Mediated Smad Signaling Pathway (TGF-beta/Smads)

The transforming growth factor beta (TGF-β) receptor-mediated Smad signaling pathway is a highly conserved cellular signaling cascade that regulates a wide range of biological processes, including cell proliferation, differentiation, apoptosis, immune regulation, and tissue homeostasis. This pathway is initiated by the binding of TGF-β family ligands (TGF-β isoforms, bone morphogenetic proteins (BMPs), and Activins) to their specific cell surface receptors (Type I and Type II serine/threonine kinase receptors) and transduced intracellularly primarily via the Smad family of proteins. Activated type I receptors phosphorylate R-Smads (Smad1/2/3/5/8), which then form heteromeric complexes with Co-Smad4 and regulate transcriptional programs. Inhibitory Smads (Smad6/7) provide negative feedback. In addition to canonical Smad-dependent signaling, activated TGF-beta receptors can trigger non-Smad pathways such as MAPK cascades, PI3K/Akt/mTOR axis, Rho GTPases.

Other names

TGF-β/Smad pathwayTGF-beta signaling pathwaySmad signaling pathway

TGF-beta pathway antagonists are under investigation for treating fibrosis/cancer/metabolic disease due to its central role in these pathologies.