Role of mTOR signalling in the control of translation initiation and elongation by nutrients.
Protein synthesis requires nutrients both as precursors (amino acids) and as a source of energy, since this process consumes a high proportion of cellular metabolic energy. Recent work has shown that both types of nutrients directly influence the activities of components of the translational machinery in mammalian cells. Amino acids positively regulate signalling through the mammalian target of the rapamycin (mTOR) pathway, although the degree of dependency on external amino acids varies between cell types. mTOR signalling modulates several key components involved in mRNA translation, in particular (via repressor proteins) the cap-binding initiation factor eIF4E, the ribosomal protein S6 kinases, and elongation factor eEF2. The branched-chain amino acid leucine is the most effective one in most cell types. It is currently unclear how mammalian cells sense prevailing amino acid levels, although this may involve intracellular amino acids. Cellular ATP levels can also influence mTOR activity. The activities of some translation factors are modulated by mTOR-independent mechanisms. Examples include the regulation of eEF2 by cellular energy levels, which may be controlled via the AMP-activated protein kinase, and the activity of the guanine nucleotide-exchange factor eIF2B, which is modulated by amino acids and metabolic fuels.
Proud
C G
CG
Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI/WTB Complex, Dundee, DD1 5EH, UK. c.g.proud@dundee.ac.uk
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D006224:Cricetinae; D020717:Eukaryotic Initiation Factor-2B / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020652:Peptide Elongation Factor 2 / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D019893:Ribosomal Protein S6 Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases
D000596:Amino Acids; D020717:Eukaryotic Initiation Factor-2B; D020652:Peptide Elongation Factor 2; D011494:Protein Kinases; C546842:MTOR protein, human; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases