 TGFβ superfamily ligands bind to a type II receptor, which recruits and phosphorylates a type I receptor.The type I receptor then phosphorylates receptor-regulated SMADs (R-SMADs) which can now bind the coSMAD SMAD4.R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression.