Regulation of protein synthesis by phosphorylation of eukaryotic initiation factor 2 alpha in intact reticulocytes and reticulocyte lysates.

Abstract

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 lystates 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. A modest concentration of phosphorylated eIF-2.alpha. can suffice to inhibit initiation, and one of the factors with which eIF-2 must interact may be rate limiting, especially when eIF-2.alpha. is phosphorylated.