Inhibitors of phosphoprotein phosphatases 1 and 2A cause activation of a 53 kDa protein kinase accompanying the apoptotic response of breast cancer cells.
Treatment of MCF-7 breast cancer cells with 50 nM okadaic acid triggers an apoptotic response which is accompanied by a 7-fold increase in the activity of a protein kinase with a relative molecular mass of 53 kDa. The activity of the kinase was stimulated by cell treatment with inhibitors of phosphoprotein phosphatase 1 and 2A, but not by stressing conditions. Okadaic acid-induced stimulation of the 53 kDa protein kinase was not abolished by coincubation of cells with cycloheximide. We conclude that stimulation of the 53 kDa protein kinase by inhibitors of phosphoprotein phosphatases involves pre-existing molecular components whose activity depends on the phosphorylation state of serine/threonine residues.
Rossini
G P
GP
Dipartimento di Scienze Biomediche, Sezione di Chimica Biologica, Università di Modena, Italy.
Pinna
C
C
Viviani
R
R
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008387:Marine Toxins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D004676:Myelin Basic Protein / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D054645:Protein Phosphatase 1; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D004676:Myelin Basic Protein; D010080:Oxazoles; D011500:Protein Synthesis Inhibitors; D019319:Okadaic Acid; C059041:calyculin A; D003513:Cycloheximide; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1