Fig. 1.

A schematic illustration on the signaling of TGF-βs and BMPs. TGF-β family molecules bind to specific type II and type I receptors. In most cells, TGF-β binds to TGFBR2 and ALK5 (also known as TGF-β receptor-1; TGFBR1), and BMPs bind to the BMP type II receptor (BMPR2), and ALK1, ALK2, ALK3 and ALK6. Activated type I receptors induce the phosphorylation of specific receptor-regulated (R-) SMADs. In general, a TGF-β signal results in SMAD2/3 phosphorylation and a BMP signal induces SMAD1/5/8 phosphorylation. Activated R-SMADs form complexes with SMAD4 that accumulate in the nucleus to regulate the expression of target genes. SMAD6 and SMAD7 are recognized as inhibitory SMADs and antagonize the TGF-β signal by inhibiting the activation of R-SMADs.