title: Staurosporine inhibits a tyrosine protein kinase in human hepatoma cell membranes.
abstract: Membranes from the human hepatoma cell line HepG2 mediate the phosphorylation on tyrosine of the asialoglycoprotein receptor. Manganese was the preferred divalent for phosphorylation although magnesium was effective at an 8-fold higher concentration. Calcium was ineffective at promoting phosphorylation and zinc was inhibitory. The protein kinase inhibitor staurosporine blocked asialoglycoprotein receptor phosphorylation on tyrosine in nanomolar concentrations (IC50 = 70 nM). In contrast another protein kinase C inhibitor, H7, was not inhibitory, suggesting that the effect of staurosporine was not mediated by protein kinase C inhibition. Concentrations of staurosporine that inhibit receptor phosphorylation by greater than 90% did not inhibit the phosphorylation of other protein substrates identified on SDS-polyacrylamide gels. These data suggest that staurosporine selectively and directly inhibits a membrane-associated tyrosine protein kinase.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: R J
authors.initials: RJ
authors.lastname: Fallon
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology*; D037263:Asialoglycoprotein Receptor; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000378:metabolism; D002413:Cations, Divalent / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D019311:Staurosporine; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
chemical_list: D000470:Alkaloids; D037263:Asialoglycoprotein Receptor; D002413:Cations, Divalent; D007546:Isoquinolines; D008565:Membrane Proteins; D010879:Piperazines; D011971:Receptors, Immunologic; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine