fig2

Figure 2. Proteolytic processing of GDF8 and GDF11 prodomains is a critical regulatory step. Proteolytic processing is necessary to pass from an unprocessed pre-pro complex protein to an active ligand able to signal. After a signal peptidase, the Furin protein recognizes and cleaves a specific motif -RXXR- between the prodomain and the mature domain. The inactive latent complex is then cleaved by the Tolloids family of protease to separate the prodomain from the active ligand. After cleavage, the prodomain is readily displaced when the mature ligand binds to the type II receptor and is likely degraded. Upon binding the type II receptor, a type I receptor is recruited and phosphorylated to activate downstream signaling pathways. The mature domain can also interact with inhibitors such as WFIKKN1, WFIKKN2, Follistatin (FS), or FSTL3.