Figure 1.

Signaling of TGF-β family members through Smad complexes. Smad proteins are central mediators of the signal transduction of TGF-β family members. Ligand binding assembles specific type II and type I receptors into heterotetramers. The type II receptor transphosphorylates (P) and activates the type I receptor, which subsequently activates receptor-regulated (R)-Smads. Activated R-Smads form heterooligomeric complexes with common-partner (co)-Smad. In the nucleus, Smad complexes interact with DNA-binding cofactors and cooperatively regulate a group of target genes. Crosstalk with other growth regulatory factors affects the specific binding patterns and transcriptional activity of Smads.