title: Selective inhibition by H7 and staurosporin of phorbol ester responses in U-937 cells.
abstract: The kinase inhibitors H7 and staurosporin dose-dependently stimulate adhesion U-937 cells to plastic but fail to inhibit the CD11b/CD18-dependent adhesion of U-937 cells induced by phorbol ester. The protein kinase C activity of U-937 cells, measured as phorbol ester-stimulated phosphorylation of pep epsilon in streptolysin-O permeabilized cells, is strongly inhibited by the kinase inhibitors. H7 and staurosporin efficiently overcome the inhibitory effect of phorbol-12,13-dibutyrate (PDBu) on leukotriene D4-induced increase in intracellular Ca2+. The results suggest that U-937 cell adhesion may be controlled by a protein kinase C isoform not sensitive to the inhibitors. In addition, the data indicate that selective pharmacological interference with different protein kinase C-mediated processes is achievable.
authors.affiliation: Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Skoglund
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology*; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology; D018821:CD18 Antigens; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004336:Drug Antagonism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D009363:Neoplasm Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013189:SRS-A / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D014407:Tumor Cells, Cultured
chemical_list: D000470:Alkaloids; D015703:Antigens, CD; D018821:CD18 Antigens; D007546:Isoquinolines; D016177:Macrophage-1 Antigen; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D010879:Piperazines; D013189:SRS-A; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium