Figure 1

The canonical activin pathway. Activin binds to activin type II receptors resulting in phosphorylation of the C terminus of Smad2 (pSmad2C) or smad3 followed by nuclear translocation with co-receptor Smad4. Follistatin binds to activin preventing binding the type II receptor. Phosphorylation at the linker region of Smad2 or smad3 occurs downstream of cytoplasmic proteins such as RAS and nuclear proteins such as cyclin dependent kinases. The effector function of phosphorylated Smad2 is dependent on the site of phosphorylation; C terminus phosphorylation resulting in tumour growth suppression and linker phosphorylation resulting in tumour growth promotion.