Smad proteins are categorized into three main classes:
Receptor-regulated Smads (R-Smads): These include Smad1, Smad2, Smad3, Smad5, and Smad8. They are directly phosphorylated by TGF-β receptors. Common-mediator Smad (Co-Smad): Smad4 is the only member of this class and it forms a complex with R-Smads to translocate to the nucleus. Inhibitory Smads (I-Smads): Smad6 and Smad7 inhibit the TGF-β signaling pathway by preventing the phosphorylation of R-Smads or by promoting receptor degradation.
