TGF-β superfamily ligands bind to receptors type I (TGF-βR-I, BMPR-I) and II (TGF-βR-I, BMPR-I) which are activated by autophosphorylation (P). Smad and p38MAPK pathways funnel these signals to the nucleus (alternative pathways include activation of ERK, JNK and some others). TGF-β branch initiates transcription through phosphorylation (P)/activation of R-Smads 2/3, whereas the BMP branch potentiates R-Smads 1/5/8. Activated R-Smad recruits Co-Smad (Smad-4) and the resulting complex enters the nucleus and induces the transcription of target genes. Inhibitory Smads (I-Smads 6/7) block the association of R-Smads with Co-Smad.