The activation of Smad proteins is tightly regulated through phosphorylation. Upon binding of TGF-β ligands to their receptors, the receptors undergo phosphorylation, which in turn phosphorylates R-Smads. These phosphorylated R-Smads then form complexes with Co-Smad (Smad4), which translocate to the nucleus to regulate gene expression. This process can be modulated by various factors, including ubiquitination and sumoylation, affecting their stability and activity.
