Figure 2

Role of Smurfs in the TGF-β/BMP pathways. TGF-β ligand stimulates heterodimerization of type I and type II Ser/Thr kinase receptors (labeled R-I and R-II), leading to phosphorylation of type I receptor by type II receptor. This recruits receptor regulated Smads (R-Smads), which become phosphorylated. Upon phosphorylation, R-Smads interact with the common Smad (co-Smad), Smad4, and the complex translocates into the nucleus, where it interacts with co-factors and stimulates transcription of genes involved in differentiation. The pathway is negatively regulated by inhibitory Smads (I-Smads), by SnoN and by Smurfs. Smurfs can interact with and ubiquitylate R-Smads and can be recruited by I-Smads to the receptor, where they induce receptor ubiquitylation and internalization. Furthermore, Smurfs are also involved in SnoN ubiquitylation, and thus are also able to act as positive regulators of this pathway.