Action of 12-O-tetradecanoylphorbol-13-acetate on Y1 adrenal cells apparently requires the regulatory subunit of type 1 cyclic AMP dependent protein kinase.
Y1 mouse adrenal tumor cells and mutants of Y1 cells (Kin 2 and Kin 8), with defects in regulatory subunit of type 1 protein kinase (R1), were assayed for steroid, growth, and plasminogen activator after application of the tumor promoter 12-O-Tetradecanoylphorbol-13-acetate (TPA). TPA, like ACTH, caused an increase in steroid production and a decrease in growth in Y1 cells. The effects on steroidogenesis were diminished in Kin 2 and markedly diminished in Kin 8. TPA induced plasminogen activator in Y1 but not Kin 2 or Kin 8 while ACTH induced the enzyme in both Y1 and Kin 2 but not Kin 8. TPA did not produce a measurable increase in cyclic nucleotides in Y1 cells. Unlike Cytochalasin E, another agent that causes steroidogenesis without changes in cyclic AMP concentration, TPA and ACTH did not require serum for its effect on steroid production. Cytochalasin E also caused induction of plasminogen activation in Y1, but not in Kin 2 or Kin 8 cells. TPA however produced growth inhibition in both mutant cell types while ACTH produced a progressively diminishing growth inhibitory effect in Kin 2 and Kin 8. The results suggest that a portion of TPA action on Y1 cells requires R1.
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis; D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D003572:Cytochalasins / Q000494:pharmacology; D051379:Mice; D010960:Plasminogen Activators / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000305:Adrenal Cortex Hormones; D003572:Cytochalasins; C007215:cytochalasin E; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D011494:Protein Kinases; D010960:Plasminogen Activators; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate