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Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033
3 To whom correspondence should be addressed. E-mail: jjefferson{at}psu.edu.
Amino acids act through a number of signaling pathways and mechanisms to mediate control of gene expression at the level of mRNA translation. This report reviews recent findings that illustrate the manner through which amino acids act to regulate the initiation phase of mRNA translation. The report focuses on signaling pathways that involve the eukaryotic initiation factor-2 (eIF2) protein kinase, general control non-derepressing kinase-2 and the mammalian target of rapamycin (mTOR) protein kinase. It also describes the mechanisms through which amino acid–induced modulation of eIF2 phosphorylation and mTOR-mediated signaling cause derepression of translation of specific mRNAs and result in an overall change in the pattern of gene expression. Finally, it provides examples of mRNAs whose translation is modulated through these mechanisms.
KEY WORDS: • mRNA leucine • upstream open reading frame • internal ribosome entry site • eukaryotic initiation factor
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