Akt and ubiquitin-proteasome signaling pathways.

<p>On the left side, upon stimulation of their respective receptor, insulin or insulin-growth factor 1 stimulates phosphorylation of Akt. Protein synthesis is then promoted through activation of p70S6K and inhibition of GSK-3β. On the right side, following stimulation by the appropriate stimuli (pro-inflammatory cytokines, oxidative stress, lipopolysaccharide, etc) NF-κB becomes activated and transcribes, among others, MuRF1. In pro-atrophic conditions, FoxO also transcribes MuRF1 and Atrogin-1. These E3-ligases increase total polyubiquitination and therefore promote protein degradation through the proteasome. Mitogen activated protein kinase p38 is also known to induce muscle protein degradation. In addition to promoting synthesis, activated Akt is an inhibitor of protein degradation by restraining nuclear translocation of FoxO. Activation = Filled arrows Inhibition = Hammer head lines Translocation = Dashed arrows.