Figure 1.

TGF-β signaling pathway TGF-β is secreted in a latent form and activation is mediated by several molecules including furin and emilin. Active TGF-β peptides (TGFB1, 2, 3) bind to the Type II receptor (TGFBR2), which recruits and activates Type I receptors such as TGFBR1 or ACVRL1. The activated Type I receptor phosphorylates receptor-specific SMAD molecules: TGFBR1 phosphorylates SMAD2 and 3, and ACVRL1 phosphorylates SMAD1, 5 and 8. These activated SMADs form a larger complex with Smad4 and translocate to the nucleus where they regulate gene transcription. Accessory receptors such as ENG have a role in the balance of ACVRL1 and TGFBR1 signaling to regulate endothelial cell proliferation. In addition to the classical SMAD signaling pathway, a SMAD-independent pathway using alternative molecules such as MAP3K7 can also mediate TGF-β signaling. TGFB: Transforming growth factor-β, TGFBR: Transforming growth factor-β receptor, EMILIN1: Elastin microfibril interfacer 1, SMAD: SMAD family member, MAP3K7: Mitogen-activated protein kinase kinase kinase 7, ENG: Endoglin, ACVRL1: Activin A receptor type II-like 1, FURIN: Furin