Protein kinases and phosphatases modulate c-fos expression in rat hepatocytes. Effects of angiotensin II and phorbol myristate acetate.
In isolated rat hepatocytes angiotensin II and phorbol 12-myristate 13-acetate (PMA) induce the expression of c-fos. We studied the possible transduction pathway(s) involved in this effect using inhibitors of serine-threonine and tyrosine protein kinases. Calphostin and staurosporine, inhibitors of protein kinase C and other serine-threonine protein kinases, block in a dose-dependent manner the effect of angiotensin II and PMA. Interestingly, genistein also blocks the induction of this proto-oncogene, suggesting a role for tyrosine protein kinases. Inhibitors of serine-threonine protein phosphatases, such as okadaic acid, microcystin LR and calyculin also induce c-fos expression. These data suggest that protein phosphatases exert a tonic inhibitory control of c-fos expression. The effect of these phosphatase inhibitors were not blocked by staurosporine, calphostin or genistein. Our results suggest that the expression of c-fos in rat hepatocytes is regulated by complex phosphorylation-dephosphorylation cascade(s) probably involving serine/threonine and tyrosine protein kinase and protein phosphatase activities.
González-Espinosa
C
C
Departamento de Bioenergética, Universidad Nacional Autónoma de México, México, D.F.
García-Sáinz
J A
JA
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004988:Ethers, Cyclic / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D008387:Marine Toxins; D052998:Microcystins; D009281:Naphthalenes; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D011083:Polycyclic Compounds / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000470:Alkaloids; D004988:Ethers, Cyclic; D007529:Isoflavones; D008387:Marine Toxins; D052998:Microcystins; D009281:Naphthalenes; D010080:Oxazoles; D010456:Peptides, Cyclic; D011083:Polycyclic Compounds; D047428:Protein Kinase Inhibitors; C061465:calphostin complex; D000804:Angiotensin II; D019319:Okadaic Acid; C059041:calyculin A; D019833:Genistein; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D010749:Phosphoprotein Phosphatases; C057862:cyanoginosin LR; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate