Inhibition of protein phosphorylation by chloroquine.
The rapid phase of fructose-1,6-bisphosphatase (FBPase) inactivation following glucose addition to starved yeast cells [reported previously] is inhibited on addition of 10 mM chloroquine (CQ) at about pH 8. This inhibition of inactivation was shown to be due to the prevention of phosphorylation of the enzyme. CQ was also found to inhibit general protein phosphorylation in the yeast cells. Glycolysis, as observed by changes in intracellular glucose-6-phosphate and extracellular glucose and ethanol concentrations, was shown to be significantly inhibited in cells treated with CQ. Similarly, a decrease in ATP concentrations was observed. However, during the early stages of phosphorylation of FBPase, levels of ATP were similar in cells containing CQ as in those without CQ. Thus, decrease in ATP levels is not thought to be significantly responsible for the inhibition of protein phosphorylation. However, the phosphorylating activity of cyclic AMP-dependent protein kinases is inhibited in vitro by relatively low concentrations of CQ. Thus, prevention of protein phosphorylation by CQ is believed to be due to inhibition of protein kinases in yeast cells.
D002738:Chloroquine / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors; D005656:Fungal Proteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism
D005656:Fungal Proteins; D047428:Protein Kinase Inhibitors; D002738:Chloroquine; D006597:Fructose-Bisphosphatase