Control of protein synthesis in human reticulocytes by heme-regulated and double-stranded RNA dependent eIF-2 alpha kinases.
Heme-deficiency and double-stranded RNA (dsRNA) activate distinct cyclic 3':5'-AMP independent protein kinases (HRI and dsI, respectively) in rabbit reticulocyte lysates. These kinases inhibit protein synthesis by phosphorylating the 38,000 daltons (38K) subunit of the initiation factor eIF-2 (eIF-2 alpha). Using separation techniques to obtain a reticulocyte enriched fraction and reticulocyte-free erythrocytes, we have prepared lysates of these fractions from normal human whole blood. Human reticulocyte-enriched lysates contain the hemin-regulated and dsRNA-dependent protein kinases which inhibit protein synthesis and which phosphorylate rabbit eIF-2 alpha. An endogenous 38K polypeptide which co-migrates with rabbit eIF-2 alpha is also phosphorylated. In contrast, human mature erythrocytes contain little or no heme-regulated or dsRNA-dependent eIF-2 alpha kinase activities which are inhibitory of protein synthesis.
D001798:Blood Proteins; D004789:Enzyme Activation; D005033:Ethylmaleimide / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2; D006418:Heme / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D010448:Peptide Initiation Factors / Q000097:blood*; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects; D011494:Protein Kinases / Q000097:blood*; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012156:Reticulocytes / Q000378:metabolism*; D019892:eIF-2 Kinase
D001798:Blood Proteins; D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D012330:RNA, Double-Stranded; D006418:Heme; D011494:Protein Kinases; D019892:eIF-2 Kinase; D005033:Ethylmaleimide