Regulation of Interferon-impaired Initiation Factor Activity in Vitro by cAMP and dsRNA

Abstract

Summary

Interferon treatment of mouse L cells causes the reduction of activity of initiation factor (eIF-2) which forms a ternary complex with Met-tRNA_f and GTP. The activity of eIF from the cells treated with interferon was specifically increased when incubated with 12 μM cAMP, but no effect of cAMP on the eIF-2 activity from untreated cells was observed. ATP (1 mM) also slightly increased the interferon-impaired eIF-2 activity. The restoration of activity of eIF-2 from interferon-treated cells was completely prevented by the addition of inhibitors of protein kinases (either aminopurine (2 mM) or a relatively high concentration (5 μg/ml) of dsRNA (poly rI:poly rC)) without a direct effect on normal eIF-2 activity. However, low concentrations of dsRNA (50 ng/ml) which activate certain protein kinases, strongly stimulated the reduction of eIF activity induced by interferon. Taken together, these observations suggest that different protein kinases may be involved in the interferon-induced reduction of eIF-2 activity and the restoration of interferon-impaired eIF-2 activity.