Inhibition of 2'‐phosphodiesterase by cAMP‐dependent protein kinase

Abstract

2'‐Phosphodiesterase from NIH 3T3 cells was purified about 530‐fold. Treatment of the cell lysate with the cAMP‐dependent protein kinase causing the 2'‐phosphodiesterase inhibition did not result in phosphorylation of the enzyme itself. The kinase was found to phosphorylate a specific 18‐kDa protein, the phosphorylated form of this protein being the inhibitor of 2'‐phosphodiesterase.

Modulation of the Antiviral 2-5A System in Human Immunodeficiency Virus-1-Infected CEM Cells by Propentofylline

“…The involvement of cAMP in the control of 2~5A metabolism has been hypothesized already (Itkes, 1994). The increase in intracellular cAMP level in the presence of the cAMP phosphodiesterase inhibitor theophylline was found to be associated with an increase in 2-5A synthetase activity and an inhibition of the 2-5A-degrading 2'-phosphodiesterase activity (Itkes et al, 1984;Itkes, 1994). There is also evidence that the antiproliferative Although it is likely in view of our resultsthat the decrease in 2-5A synthetase activity and protein following HIV infection is due to the HIV-caused decrease in 2-5A synthetase mRNA level, proteolytic degradation of the enzyme might be possible, too.…”

Regulation of the 2′,5′‐Oligoadenylate System by Cyclic Adenosine Monophosphate‐Dependent Phosphorylation

“…Highly purified phosphodiesterase of 2-5A (2'-PDE) was isolated from L-cells, mouse reticulocytes (31), and NIH 3T3 cells (32). The molecular weight of the enzymes from L-cells and reticulocytes was 35,000-40,000 (31) and of the enzyme from NIH 3T3 cells was 46,000 (32).…”

Crystallization and preliminary X-ray crystallographic analysis of human phosphodiesterase 12

“…PDE12, an enzyme that belongs to the endonuclease/exonuclease/ phosphatase family, hydrolyzes 2-5A to ATP and AMP and is therefore also referred to as 2 0 ,5 0 -phosphodiesterase (2 0 ,5 0 -PDE; Itkes et al, 1984;Alster et al, 1986;Torrence et al, 1987;Johnston & Hearl, 1987;Kubota et al, 2004). It plays a role as a negative regulator in the 2-5A system by reducing 2-5A levels in cells.…”