Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine

Numerous reports established that in skeletal muscle the indispensable bran ched-chain amino acid leucine is unique in its ability to initiate signal t ransduction pathways that modulate translation initiation. Oral administrat ion of leucine stimulates protein synthesis in association with hyperphosph orylation of the translational repressor, eukaryotic initiation factor (eIF ) 4E binding protein 1 (4E-BP1), resulting in enhanced availability of the mRNA cap-binding protein eIF4E, for binding eIF4G and forming the active eI F4F complex. In addition, leucine enhances phosphorylation of the 70-kDa ri bosomal protein S6 kinase (S6K1). These results suggest that leucine upregu lates protein synthesis in skeletal muscle by enhancing both the activity a nd synthesis of proteins involved in mRNA translation. The stimulatory effe cts of leucine on translation initiation are mediated in part through the p rotein kinase mammalian target of rapamycin (mTOR), where both insulin sign aling and leucine signaling converge to promote a maximal response.