TGFB/SMAD signaling pathway

The TGF-β/SMAD signaling pathway. (A) Ligand binding: A heteromeric complex is formed with an interaction of type II, type I receptors, and TGF-β ligands. (B) Activation of receptor: Ligand binding stimulates the type II receptor to phosphorylate and activate the type I receptor. (C) Activation of R-SMADs: Once the type I receptor is activated, it initiates phosphorylation and activation of the receptor-activated SMADs (R-SMADs, SMAD2, and SMAD3 for TGF-β signal). (D) Inhibition of R-SMAD activation: Inhibitory SMADs, SMAD7, and SMAD6 compete with R-SMADs to intervene with the type I receptor. As a result, R-SMAD activation and transmission of the SMAD signaling is prevented. (E) The complex of R-SMADs and CO-SMAD formation: Activated R-SMADs dissociate from type I receptors to form a complex with the common mediator, CO-SMAD, SMAD4. (F) The complex of R-SMAD and SMAD4 can translocate from cytoplasm to nucleus and bind to transcription factors, resulting in the transcription of target genes. Here, SMAD1, SMAD5, and SMAD8 are shown for BMP signal. Adapted from Molecular Biology of Human Cancers (Springer 2005) [28]

Publication

Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors (2024) Farhana Runa, et al. Pharmaceuticals (Basel). 2024 Mar;17(3). Figure: F1. Homo sapiens

Disease mentions