Double-stranded RNA inhibits a phosphoprotein phosphatase present in interferon-treated cells.
In accord with previous studies, (I)n . (C)n, a potent inhibitor of the cell-free protein-synthesizing system of interferon-treated L cells, stimulates incorporation of 32P from [gamma-32P]ATP into the 67,000-dalton protein, P1. The double-stranded RNA (I)n . (br5C)n, which is inactive as an inhibitory of protein synthesis, does not stimulate phosphorylation of P1 under conditions approximating those of protein synthesis. However, we have found conditions under which (I)n . (br5C)n is approximately as effective as (I)n . (C)n in stimulating incorporation of label from [gamma-32P]ATP into 67,000-dalton protein. Upon transfer of labeled P1 from these conditions to those compatible with protein synthesis, there is a time-dependent decrease in label in the 67,000-dalton protein. This decrease is more rapid in the presence of (I)n . (br5C)n than in the presence of (I)n . (C)n. This differential decrease is also observed when 32P-labeled extracts are diluted into buffer containing 10 mM ATP, hexokinase and 1 and M glucose, or Escherichia coli alkaline phosphatase. A partial proteolytic digest of P1 labeled in the absence of double-stranded RNA or in the presence of (I)n . (C)n or (I)n . (br5C)n gives rise to similar peptide patterns. These results suggest that dephosphorylation as well as phosphorylation determines the net incorporation of 32P into P1. Moreover, these results suggest the existence of a phosphatase activity that may be inhibited more strongly by (I)n . (C)n than by (I)n . (br5C)n.
D000818:Animals; D007372:Interferons / Q000494:pharmacology*; D007739:L Cells; D051379:Mice; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D012269:Ribosomal Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship
D012330:RNA, Double-Stranded; D012269:Ribosomal Proteins; D007372:Interferons; D010749:Phosphoprotein Phosphatases; D011070:Poly I-C