Molecular mechanisms of control of protein biosynthesis.

Reticulocytes contain two protein kinases which, when activated, phosphorylate the alpha subunit of the chain initiation factor eIF-2 interfering with its function. One kinase is activated in the absence of heme, the other is activated by low concentrations of double-stranded RNA. Both appear to be active in a phosphorylated form. Phosphorylation of the eIF-2 alpha subunit does not modify the basic properties of the factor but prevents its interaction with a stimulating protein (SP) required for binary complex formation at low, physiological concentrations of eIF-2 and Mg 2+. SP, isolated in the form of an eIF-2 complex (eIF-2. SP) of high molecular weight (approximately 450000), promotes formation of a GTP . eIF-2 binary complex, the first step of initiation, in a catalytic fashion. The available evidence suggests that eIF-2 . SP can form in the presence of Mg 2+ a GTP . eIF-2 . SP complex that interacts with free eIF-2 forming GTP . eIF-2 (binary complex) and eIF-2. SP.