Activins and activin antagonists in hepatocellular carcinoma

Figure 1 Graphic representation of activin signaling and interaction points with activin antagonists. A: Activin dimers first bind the type II activin receptors, which then recruit and phosphorylate typeIreceptors. These in turn phosphorylate receptor-activated Smads, which subsequently form a complex with Smad 4 and are translocated to the nucleus, where they regulate the transcription of target genes; B: Activin antagonists can block activin signals by: (1) Binding activins in the extracellular space like follistatin or FLRG and thereby blocking their access to activin receptors; (2) Acting as inhibitory co-receptors, which prevent ligand receptor interactions (Cripto) or receptor dimerization (BAMBI); (3) Competing with receptor-activated Smads 2 and 3 for binding sites on activin receptors (Smad 7).