The effects of triethyltin bromide on red cell and brain cyclic AMP-dependent protein kinases.
Triethyltin bromide activates the cyclic AMP-dependent protein kinases of human red cell membranes and of bovine brain. Additions of 25-500 microM triethyltin to red cell ghosts resulted in enhanced phosphorylation of ghost proteins. When added to partially purified cyclic AMP-dependent protein kinases from red cell ghosts or bovine brain, stimulation of the phosphorylation of calf thymus histone was observed. The enhancement of kinase activity was due to release of catalytic subunits from the intact protein kinase. Brief exposure of the partially purified enzymes to triethyltin, followed by DE52 chromatography, resulted in elution profiles for regulatory and catalytic subunits that were similar to the profile resulting after cyclic AMP activation. Triethyltin interacts with both regulatory and catalytic subunits. When it was added to the partially purified cyclic AMP-dependent protein kinases from human red cell ghosts or bovine brain, noncompetitive inhibition of cyclic AMP binding to the regulatory subunit of the enzyme was observed. It interacted with the catalytic subunit to produce slow inhibition of catalytic activity. The inhibition was non-competitive with respect to both histone and ATP. When intact red cells were subjected to brief exposure with triethyltin, enhanced phosphorylation of certain membrane proteins occurred, suggesting that the activation of the cyclic AMP protein kinases by triethyltin may be physiologically significant.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology*; D046911:Macromolecular Substances; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D014267:Triethyltin Compounds / Q000494:pharmacology*
D046911:Macromolecular Substances; D014220:Trialkyltin Compounds; D014267:Triethyltin Compounds; D000242:Cyclic AMP; D011494:Protein Kinases; C026405:bromotriethylstannane