Staurosporine inhibits the soluble and membrane-bound protein tyrosine kinases of human neutrophils.
Superoxide production by neutrophils triggered with a chemotactic peptide or a phorbol ester is inhibited by the protein kinase antagonists staurosporine or 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). We evaluated the effects of these antagonists on the protein tyrosine kinases and protein kinase C activities of neutrophils. Staurosporine completely inhibited all of these enzymes, whereas 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine was only substantially effective against protein kinase C. Thus, if a protein tyrosine kinase is involved in superoxide production, it is likely to function with a second kinase sensitive to 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine.
Badwey
J A
JA
Department of Cell and Molecular Biology, Boston Biomedical Research Institute, MA 02114.
Erickson
R W
RW
Curnutte
J T
JT
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D009504:Neutrophils / Q000201:enzymology*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000097:blood*; D019311:Staurosporine
D000470:Alkaloids; D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine