Regulation of protein synthesis.

Synthesis of globin in reticulocyte lysates depends on the presence of heme, the prosthetic group of hemoglobin. In the absence of heme, an inhibitor of polypeptide chain initiation is activated. The inhibitor is a cyclic AMP-independent protein kinase that catalyzes the phosphorylation by ATP of the small subunit of the initiation factor eIF-2. This blocks the interaction of eIF-2 with eIF-2-stimulating protein (ESP) that is essential for initiation. Our observations are consistent with the view that the inhibitor is activated by phosphorylation catalyzed by a cyclic AMP-dependent protein kinase. Heme inhibits this enzyme and, in this way, prevents activation of the inhibitor of chain initiation.