Fig. 2

CD109 and TGF-β signaling. TGF-β binds the TGF-βR2, which recruits and phosphorylates the TGF-βR1. Activated TGF-βR1 propagates the signal downstream by directly phosphorylating Smad2 and Smad3. Phosphorylated R-SMADs then form heteromeric complexes with Smad4, combined with transcription factors, regulate gene transcription and cell function. TGF-β receptors internalize via the clathrin-coated pits or the caveolar pathway. CD109 increases TGF-β binding to TGF-β receptors and promotes TGF-β receptor localization to the caveolae, ultimately increases TGF-β receptor endocytosis and facilitates TGF-β receptor degradation. The inhibitory effects of CD109 require Smad7 expression and Smurf2 ubiquitin ligase activity