We analyzed the signaling processes initiating proteolytic events in the human soleus muscle during short-term exposure under the non-weight-bearing conditions. Dry immersion (DI) was used to induce weight deprivation in the m. soleus for 3 days. Western blotting was used to determine the level of insulin receptor substrate 1 (IRS-1), total and phosphorylated neuronal NO synthase (nNOS), and adenosine monophosphate-activated protein kinase (AMPK), which control the anabolic and catabolic signaling pathways, and the level of cytoskeletal protein desmin and Са2+-activated protease calpain. By day 3 of DI, calpain- dependent proteolysis manifests itself by reductions in both the total content and level of nNOS phosphorilation. The rate of AMPK phosphorylation was significantly decreased. © 2017, Pleiades Publishing, Inc.