REGULATION OF PROTEIN-SYNTHESIS BY HEME-REGULATED EIF-2-ALPHA KINASE

Protein synthesis is regulated by the phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (elF-2 alpha) in a variety of cells. At present, there are two distinct mammalian elF-2 alpha kinases that have been cloned, the double-stranded-RNA-dependent elF-2 alpha kinase (PKR) and the heme-regulated elF-2 alpha kinase (HRI). HRI is activated under conditions of heme deficiency in immature erythroid cells, and its activity is inhibited by heme. The high levels of HRI in reticulocytes indicate that its major physiological role is the regulation of protein synthesis, particularly of hemoglobin, according to the concentration of heme in these cells.