Two major Smad pathways in TGF‐β superfamily signalling

Members of the transforming growth factor-beta (TGF-beta) superfamily bind to two different serine/threonine kinase receptors, i.e. type I and type II receptors. Upon ligand binding, type I receptors specifically activate intracellular Smad proteins. R-Smads are direct substrates of type I receptors; Smads 2 and 3 are specifically activated by activin/nodal and TGF-beta type I receptors, whereas Smads 1, 5 and 8 are activated by BMP type I receptors. Nearly 30 proteins have been identified as members of the TGF-beta superfamily in mammals, and can be classified based on whether they activate activin/TGF-beta-specific R-Smads (AR-Smads) or BMP-specific R-Smads (BR-Smads). R-Smads form complexes with Co-Smads…