Modulation of Smad activation. (a) Activated TβRI recruits and phosphorylates Smad2/3 at the C-terminal, and then the phosphorylated Smad2/3 binds Smad4 to form a Smad heterocomplex to mediate signal transduction. Endofin recruits Smad4 to the receptor complex in early endosomes and facilitates the association of receptor-activated Smad2/3 with Smad4. (b) BAMBI forms a ternary complex with receptors and Smad7 and inhibits the interaction between TβRI and Smad3, impairing Smad3 activation. PM: plasma membrane.
