Regulation of protein synthesis by phosphorylation of eukaryotic initiation factor 2 alpha in intact reticulocytes and reticulocyte lysates.
Studies in intact rabbit reticulocytes and reticulocyte lysates provide further evidence of a functional role for the phosphorylation of eukaryotic initiation factor 2 alpha (eIF-2 alpha) in the regulation of initiation of protein synthesis in eukaryotic cells. In intact reticulocytes treated with isonicotinic acid hydrazide to inhibit heme synthesis, the phosphorylation of eIF-2 alpha was significantly greater than in control cells. In heme-deficient reticulocyte lysates and in lysates treated with double-stranded RNA, significant phosphorylation of eIF-2 alpha occurred prior to the onset of inhibition of protein synthesis; a large proportion, however, of the total eIF-2 alpha remained unphosphorylated. These findings indicate that a modest concentration of phosphorylated eIF-2 alpha can suffice to inhibit initiation, and they suggest that one of the factors with which eIF-2 must interact may be rate limiting, especially when eIF-2 alpha is phosphorylated.
D000818:Animals; D002625:Chemistry, Organic; D004591:Electrophoresis, Polyacrylamide Gel; D006418:Heme / Q000172:deficiency; D006427:Hemin / Q000494:pharmacology; D007700:Kinetics; D055601:Organic Chemistry Phenomena; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism*
D010448:Peptide Initiation Factors; D006418:Heme; D006427:Hemin