Effect of hemin on site-specific phosphorylation of eukaryotic initiation factor 2.

Abstract
Initiation factor 2 (eIF-2) is phosphorylated in vitro by 2 different cyclic nucleotide-independent protein kinases. As previously shown, a protein kinase activity that comigrates with the major casein kinase activity from rabbit reticulocytes phosphorylates eIF-2.beta.. A 2nd protein kinase that specifically phosphorylates eIF-2.alpha. was identified. Both protein kinase activities demonstrate cyclic nucleotide-independent activity and are not inhibited by the protein diagnostic for cyclic AMP-regulated protein kinase activities. Phosphorylation of eIF-2.alpha. is almost completely inhibited by 20-35 .mu.M hemin, whereas phosphorylation of eIF-2.beta. is only partially inhibited. Hemin acts by decreasing the rate of incorporation of phosphate into eIF-2.alpha.. The protein kinase activity that modifies eIF-2.alpha. was shown to have inhibitory activity in the cell-free protein-synthesizing system, whereas the protein kinase for eIF-2.beta. has no effect. The identity of the former enzyme with the hemin-controlled repressor and role of hemin in the control of initiation are discussed.

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