Phosphorylation of eukaryotic initiation factor-2 (elF-2) is an important mechanism regulating general translation initiation. Two mammalian elF-2 kinases, the double-stranded-RNA-dependent kinase (PKR) and hemeregulated inhibitor kinase (HRI), have been characterized by sequencing, revealing shared sequence and structural features distinct from other eukaryotic protein kinases. Recent work in yeast has shown that a third related kinase, GCN2, also phosphorylates the regulated site in elF-2. However, unlike the mammalian kinases, this kinase regulates genespecific translation. Current models are presented for the regulation of each elF-2 kinase, and the molecular basis for how this general form of regulation is adapted to control expression of a single species of messenger RNA is discussed.
ASJC Scopus subject areas
- Molecular Biology