2-Aminopurine inhibits the double-stranded RNA-dependent protein kinase both in vitro and in vivo.
The autophosphorylation of interferon (IFN)-induced double-stranded RNA-dependent p68 protein kinase (PKR) and phosphorylation of the alpha-subunit of the translation initiation factor eIF-2 were inhibited by 10 mM 2-aminopurine in vitro. High concentrations of ATP overcame the inhibition. Kinetic studies indicated that 2-aminopurine is a competitive inhibitor with respect to ATP, suggesting that these two molecules bind the same site on the kinase. Treatment of HeLa cells with poly(I):poly(C) stimulated PKR autophosphorylation in vivo. The stimulated activity was inhibited by 10 mM 2-aminopurine to approximately the same extent as the in vitro inhibition.
Hu
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Department of Biochemistry, University of Iowa, Iowa City 52242.
Conway
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TW
D015075:2-Aminopurine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D019892:eIF-2 Kinase
D015075:2-Aminopurine; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase