Probing the role of homomeric and heteromeric receptor interactions in TGF-β signaling using small molecule dimerizers

Background: Transforming growth factor β (TGF-β) arrests many cell types in the G1 phase of the cell cycle and upregulates plasminogen activator inhibitor 1 (PAI-1). The type I (TGF-βRI) and II (TGF-βRII) TGF-β receptors mediate these and other effects of TGF-β on target cells. TGF-β initially binds to TGF-βRII and subsequently TGF-βRI is recruited to form a heteromeric complex. TGF-βRI phosphorylates the downstream effectors Smad2 and Smad3, leading to their translocation into the nucleus. Here, we explored the role of receptor oligomerization in TGF-β signaling.