Multistep regulatory system for activation of a cyclic AMP-independent eukaryotic initiation factor 2 kinase.

Three functionally related components that block peptide initiation have been identified in lysates of rabbit reticulocytes. The components function consecutively in a cascade type sequence of reactions to cause phosphorylation of eukaryotic peptide initiation factor 2 (eIF-2). The eIF-2 kinase activated as part of this sequence has been tentatively identified as the same protein kinase that is activated by heme deficiency as part of the hemin-controlled repressor (HCR) system. The first component in the sequence is heat stable and can be reversibly activated by heat or pressure. It activates a second, heat-labile, component that in turn directly or indirectly activates the hemin-controlled eIF-2 kinase. This heat-labile component appears to function through proteolysis. This reaction sequence is not detectably affected by heme or cyclic AMP and thus appears to provide an alternative mechanism, independent of heme, for activation of the cyclic AMP-independent eIF-2 kinase of the HCR system.