%0 Journal Article
%T Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway
%A Agus Suryawan
%A Hanh V Nguyen
%A Rosemarie D Almonaci
%A Teresa A Davis
%J Journal of Animal Science and Biotechnology
%D 2012
%I BioMed Central
%R 10.1186/2049-1891-3-3
%X One of the hallmarks of the neonatal period is rapid growth, which is due to a high rate of protein synthesis [1]. We previously showed in neonatal pigs that the high rate of deposition of proteins, especially in skeletal muscle, is in part due to their ability to increase protein synthesis in response to feeding, a response that significantly declines with development [2]. We further demonstrated that the feeding-induced stimulation of protein synthesis in most tissues is independently regulated by insulin and amino acids [3]. Among amino acids, we found that leucine alone can stimulate protein synthesis in neonatal pigs and this effect decreases with development [4,5]. However, the molecular mechanism underlying the effect of leucine on the stimulation of protein synthesis in vivo is not completely known.Mammalian target of rapamycin (mTOR) is a nutrient- and hormone-sensitive kinase that plays a major role in cell metabolism, including protein synthesis [6,7]. The kinase mTOR exists in two structurally and functionally distinct complexes referred to as mTOR complex 1 (mTORC1) and mTORC2 [6]. Considerable evidence indicates that mTORC1 is rapamycin sensitive while mTORC2 is rapamycin insensitive. The main function of mTORC1 is to regulate mRNA translation by directly phosphorylating two down-stream substrates, ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1). S6K1 is a kinase for ribosomal protein S6 (rpS6) and its activation by S6K1 is crucial for mRNA translation. Furthermore, a phosphorylated form of 4E-BP1 releases eIF4E from the inactive eIF4EĦ¤4E-BP1 complex, allowing the formation of the active eIF4GĦ¤eIF4E complex to participate in translation initiation [8]. The second complex, mTORC2, has been postulated to regulate the activation of protein kinase B (PKB) [6]. The exact mechanisms by which nutrients/amino acids, especially leucine, activate mTORC1 have been partly elucidated using cell culture syste
%K leucine
%K mTORC1
%K neonatal pigs
%K rapamycin
%K skeletal muscle
%U http://www.jasbsci.com/content/3/1/3