Fig. 2.

Pathways modulating skeletal muscle protein balance. Signals from various anabolic stimuli enter the cell via membrane transporters (i.e., amino acids) or receptors (i.e., IGF-I). Amino acids induce mTOR translocation and activation at the lysosomal surface via the Rag family of proteins and the GTP loading of Rheb. In contrast, signal transduction of IGF-I and insulin binding to their cognate receptors converge at Akt to either activate mTOR at the lysosome via TSC1· TBC complex phosphorylation and subsequent Rheb-GTP loading. Upon lysosomal translocation and activation, mTOR phosphorylates several downstream targets, including 4E-BP1 and S6K1. Phosphorylation of 4E-BP1 and S6K1 enhances translation initiation, while other factors may stimulate protein elongation.