Figure 7

Schematic diagram of MST1's function in mediating fast skeletal muscle atrophy. Within an innervated myofiber, Akt kinase is active and MST1 kinase amount is restricted at low level. Thus FOXO3a is phosphorylated by Akt at multiple sites (Thr32, Ser253 and Ser315) [53], and is restricted within the myofiber cytosol through interaction with 14-3-3 proteins. Denervation induces rapid up-regulation of MST1 kinase. MST1 phosphorylates FOXO3a at Ser207 and causes its translocation into myofiber nucleus to activate expression of LC3 and Atrogin-1 genes, which leads to rapid muscle mass loss during the progression of muscle atrophy.