Purification and characterization of a protein inhibitor from rat liver that inhibits type 1 protein phosphatase when 3-hydroxy-3-methylglutaryl CoA reductase is the substrate.
A protein inhibitor of HMG-CoA reductase phosphatase activity from rat liver was purified to homogeneity. The protein was purified 4,000-fold with an overall yield of 4%. The purified protein had a molecular mass of 31 kDa. This spontaneously active protein is thermostable and acid-resistant. The protein inhibitor is phosphorylated by glycogen synthase kinase-3 and cAMP-dependent protein kinase without change in its inhibitory activity. The inhibition caused by this inhibitor on phosphatases 1 and 2A is similar to that of inhibitor-2 from rabbit skeletal muscle using hydroxymethylglutaryl-CoA reductase as substrate. The regulation properties of this inhibitor towards phosphatase 1 together with another protein inhibitor of phosphatase 2A in cholesterol metabolism are discussed.
Serra
D
D
Unit of Biochemistry, University of Barcelona School of Pharmacy, Spain.
Asins
G
G
Hegardt
F G
FG
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000302:isolation & purification; D006903:Hydroxymethylglutaryl CoA Reductases; D066298:In Vitro Techniques; D008099:Liver / Q000032:analysis; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D011506:Proteins / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D013379:Substrate Specificity
D004791:Enzyme Inhibitors; D011506:Proteins; D006903:Hydroxymethylglutaryl CoA Reductases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2