Effect of hemin on site-specific phosphorylation of eukaryotic initiation factor 2.
Initiation factor 2 (eIF-2) is phosphorylated in vitro by two 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-2beta. In addition, a second protein kinase that specifically phosphorylates eIF-2alpha has been identified. Both protein kinase activities demonstrate cyclic nucleotide-independent activity and are not inhibited by the inhibitor protein diagnostic for cyclic AMP-regulated protein kinase activities. Phosphorylation of eIF-2alpha is almost completely inhibited by 20--35 muM hemin, whereas phosphorylation of eIF-2beta is only partially inhibited. Hemin acts by decreasing the rate of incorporation of phosphate into eIF-2alpha. The protein kinase activity that modifies eIF-2alpha has been shown to have inhibitory activity in the cell-free protein-synthesizing system, whereas the protein kinase for eIF-2beta 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.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D005914:Globins / Q000096:biosynthesis; D006160:Guanosine Triphosphate / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism
D010448:Peptide Initiation Factors; D010710:Phosphates; D006418:Heme; D006427:Hemin; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D005914:Globins; D011494:Protein Kinases; D008274:Magnesium; D011188:Potassium
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