Regulation of protein synthesis in rabbit reticulocyte lysates. Thiophosphorylation of initiation factor eIF-2 by heme-regulated protein kinase.

The heme-regulated protein kinase, which specifically phosphorylates the 38-kDa subunit of initiation factor eIF-2, can utilize adenosine 5'-O-(3-thiotriphosphate) (ATP[gamma S]) as a substrate. The rate of thiophosphorylation is 5-6-times slower than that observed with ATP. It is of special interest that thiophosphorylated derivatives of eIF-2 are resistant to dephosphorylation catalyzed by eIF-2 phosphoprotein phosphatase. The thiophosphorylated eIF-2 is less effective in promoting protein synthesis in hemin-deficient lysates under physiological conditions. In addition, ATP[gamma S] could also be utilized by the self-phosphorylation activity intrinsically associated with HRI.