Abstract
Phosphorylation of eIF-2α is the best characterized mechanism to regulate translation initiation in eukaryotic cells. Three protein kinases have been identified that specifically phosphorylate eIF-2α on serine-51. The mammalian PKR and HRI kinases are activated in response to viral infection or low heme levels, respectively, and function to shut off protein synthesis in mammalian cells under these stress conditions (reviewed in ref. 1). The yeast GCN2 kinase is activated under amino acid starvation conditions and phosphorylates yeast eIF-2α (encoded by the SUI2 gene) on serine-51 (2). In the yeast Saccharomyces cerevisiae phosphorylation of eIF-2α not only inhibits general translation initiation, but due to the unique arrangement of upstream open reading frames (uORFs) in the leader of the GCN4 mRNA, phosphorylation of eIF-2α stimulates GCN4 expression (reviewed in refs. 3 and 4). A modest increase in the levels of eIF-2α phosphorylation is sufficient to stimulate GCN4 expression, while the slow-growth phenotype due to inhibition of general translation initiation requires higher levels of eIF-2α phosphorylation (2,5,6). The ability to use reporters sensitive to both low levels (GCN4 expression) and high levels (growth rate) of eIF-2α phosphorylation makes S cerevisiae an ideal system to study eIF-2α phosphorylation.
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Dever, T.E. (1998). Analysis of elF-2α Kinases in Yeast. In: Martin, R. (eds) Protein Synthesis. Methods in Molecular Biology, vol 77. Springer, Totowa, NJ. https://doi.org/10.1385/0-89603-397-X:167
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DOI: https://doi.org/10.1385/0-89603-397-X:167
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