Smad proteins are categorized into three classes: receptor-regulated Smads (R-Smads), common mediator Smads (Co-Smads), and inhibitory Smads (I-Smads). R-Smads, such as Smad2 and Smad3, are activated by phosphorylation upon TGF-β receptor binding. Co-Smad, primarily Smad4, partners with R-Smads to form complexes that translocate into the nucleus. I-Smads, like Smad7, serve as negative regulators by preventing R-Smad activation and promoting their degradation.
