Figure 6.

Schematic of SMAD-independent and SMAD-independent TGF-β1 signaling pathways in IBD. (A) In the canonical pathway, the TGF-β1 ligand binds to the TβRII receptor. Activated TβRI can phosphorylate a group of transcription factors, including SMAD2 and SMAD3 on C-terminal serine. Consequently, a trimeric complex containing SMAD2, SMAD3, and SMAD4 was formed. This complex translocates into the nucleus, where it induces or inhibits target gene expression. In addition to the canonical TGF-β1 signaling pathway, TGF-β type I and II receptors can also activate downstream non-canonical pathways, including PI3K/AKT signaling pathway, in an SMAD-independent manner.