 There are essentially two intracellular pathways involving these R-SMADs.TGF beta's, Activins, Nodals and some GDFs are mediated by SMAD2 and SMAD3, while BMPs, AMH and a few GDFs are mediated by SMAD1, SMAD5 and SMAD9.The binding of the R-SMAD to the type I receptor is mediated by a zinc double finger FYVE domain containing protein.