Figure 1.

The TGF-β signalling pathway. Binding of an activated TGF-β ligand to TGFR-2 recruits and activates TGFR-1. This, in turn, phosphorylates Smad2 and/or Smad3 (R-Smads), which then form complexes with Smad4 (Co-Smad) and translocate into nucleus to regulate the transcription of various target genes. Smad7 (I-Smad) inhibits the pathway through various mechanisms, including mediating the degradation of TGFR-1, inhibiting phosphorylation of Smad2/Smad3 or inhibiting the formation of the Smad2/3-Samd4 complex. In addition to the canonical Smad-dependent signalling, activated TGF-β receptors can trigger other signalling pathways including ERK-MAPK, p38-MAPK, PI3K-Akt and JNK.