ACTH inhibits A Ras-dependent anti-apoptotic and mitogenic pathway in mouse Y1 adrenocortical cells.
Mouse Y1 adrenocortical tumor cells harbor amplified and overexpressed c-Ki-ras gene, displaying relatively high constitutive levels of Ras x GTP. Here we report that Y1 cells also constitutively display high levels of phosphorylated AKT/PKB, that are dependent on Ras x GTP and PI3K. ACTH rapidly causes dephosphorylation of AKT/PKB in a cAMP/PKA dependent maner. This ACTH inhibition of the anti-apoptic and mitogenic AKT/PKB pathway is likely to be relevant in ACTH growth inhibitory effects in Y-adrenocortical cells.
Forti
F L
FL
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Brasil.
Armelin
H A
HA
D000302:Adrenal Cortex / Q000166:cytology / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008934:Mitogens / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology; D013449:Sulfonamides; D014407:Tumor Cells, Cultured; D000077191:Wortmannin; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
D000324:Adrenocorticotropic Hormone; D000730:Androstadienes; D017868:Cyclic AMP-Dependent Protein Kinases; D003907:Dexamethasone; D004791:Enzyme Inhibitors; D016222:Fibroblast Growth Factor 2; D005938:Glucocorticoids; D007546:Isoquinolines; D008934:Mitogens; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras); D013449:Sulfonamides; D000077191:Wortmannin; D018631:ras Proteins; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide