The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans.

Abstract

Covalent modification of translational machinery components by phosphorylation is a principal means of regulating protein synthesis in eukaryotic cells (1). Initiation of mRNA translation is a slow step in the protein synthesis pathway (2-5). A key protein factor required for translation initiation is eIF-2. Phosphorylation of the a subunit of protein synthesis initiation factor eIF-2 (eIF-Sa)' is one of the best characterized translational control mechanisms, both in lower and higher eukaryotes. The phosphorylation of eIF-Pa on serine 51 leads to an inhibition of translation (2,4). Protein kinases that catalyze the phosphorylation of eIF-2a have been identified and characterized from a variety of eukar- yotes, ranging from yeast to human cells. The eIF-2a kinases are CAMP-independent enzymes whose induction and activation are finely regulated (Fig. 1). Dependent upon the type of cell, stimuli ranging from cytokine treatment and viral infection to the avail- ability of metabolites and cofactors required for cell function may modulate eIF-2a kinase activity (2,4,6-10). This review examines what is now known about three kinds of eIF-2a protein kinases: HRI, the acid availability.