Figure 4.

Activin and myostatin transduction signalling (A) and binding proteins (B) in myometrial system. Activin or myostatin first binds to type II receptors, and only binds type I receptors once bound to type II receptors. Within the receptor complex, type II receptors phosphorylate, and thereby activate, type I receptors, which in turn phosphorylates intracellular substrates such as the Smad proteins which mediate transcriptional regulation of activin target genes. Activin signalling is also regulated by several membrane (Cripto) and extracellular factors, including the activin-binding proteins, follistatin and FLRG. The higher expression of the binding proteins in leiomyoma may produce reduced sensitivity to the anti-proliferative effects of activin and myostatin on myometrial cells and therefore contribute to leiomyoma formation.