A defect in protein turnover underlies multiple forms of cell atrophy. Since S6 kinase (S6K) deficient cells are small and display a blunted response to nutrient and growth factor availability, we have hypothesized that mutant cell atrophy may be triggered by a change in global protein synthesis. By using mouse genetics and pharmacological inhibitors targeting the mTOR/S6K pathway, here we evaluate the control of translational target phosphorylation and protein turnover by the mTOR/S6K pathway in skeletal muscle and liver tissues. The phosphorylation of ribosomal protein S6 (rpS6), eIF4B and eEF2 are predominantly regulated by mTOR in muscle cells. Conversely in liver the MAPK and PI3K pathways also play an important role, suggesting a tissue specific control. S6K deletion in muscle mimics the effect of the mTOR inhibitor rapamycin on rpS6 and eIF4B phosphorylation without affecting eEF2 phosphorylation. To gain insights on the functional consequences of these modifications, methionine incorporation and polysomal distribution are assessed in muscle cells. Rates and rapamycin sensitivity of global translation initiation are not altered in S6K deficient muscle cells. In addition two major pathways of protein degradation, autophagy and the expression of the muscle-specific atrophy-related E3 ubiquitin ligases, are not affected by S6K deletion. Our results do not support a role of global translation control in the growth defect due to S6K deletion, suggesting specific modes of growth control and translational target regulation downstream of mTOR.