Figure 1.

The logic of TGFβ signalling from the membrane to nucleus. Upon ligand binding, the TGFβ/BMP receptor kinases mediate the phosphorylation of R-SMADs. R-SMADs are depicted showing their MH1/Linker/MH2 domains. This induces the association of R-SMADs with SMAD4 and their nuclear translocation. In the nucleus, the SMADs form transcription complexes with multiple cofactors and regulate the transcription of multiple target genes. Most of the known transcriptional cofactors of SMADs are indicated, although not all are described in the text.