Figure 1

Signal transduction through activin receptors. Activin, myostatin and GDF11 signal through type II and type I serine/threonine kinase receptors. Type IIR is the principal ligand binding receptors, and ligand/typeIIR complexes recruit and associate with type IR. Type IR is phosphorylated and activated by type IIR kinase. Smad2 and 3, activin/TGF-β specific Smads, are phosphorylated by activated type IR. In the nucleus, Smad2/3/4 complexes regulate gene expression with additional transcriptional cofactors. Smad-independent pathway such as MAPK is also activated downstream of activin receptors. Inhibin acts antagonistic to activin by forming high affinity complexes with ActRII and betaglycan. Follistatin, myostatin propeptide and receptor ectodomain inhibit the activities of activin and related factors in the extracellular space to prevent ligand/receptor interaction. Chemical type IR kinase inhibitors act in the cell to disrupt receptor/intracellular signaling.