Signal transduction of the TGF-β superfamily

A negative feedback loop is generated by the transcription of the inhibitory Smads by signaling from TGF-β family of ligands (Smad6 preferentially inhibits the BMP/Smad1 pathways, whereas Smad7 appears to act as a more general inhibitor, at least in part by associating with activated type 1 receptors to prevent R-Smad binding). The orphan receptors ALK-1 and ALK-7 are illustrated at the site of their known Smad interactions. For clarity, many other regulatory and interacting pathways are not illustrated.