Wortmannin and 1-butanol block activation of a novel family of protein kinases in neutrophils.
Neutrophils contain four uncharacterized protein kinases with molecular masses of ca. 69, 63, 49 and 40 kDa that are rapidly activated upon stimulation of these cells with the chemoattractant fMet-Leu-Phe [Ding, J. and Badwey, J.A. (1993) J. Biol. Chem. 268, 17326-17333]. We now report that wortmannin and 1-butanol block activation of all four of these kinases. These reagents are known to inhibit superoxide generation in neutrophils stimulated with this agonist. Wortmannin inhibits phosphatidylinositol 3-kinase and blocks activation of phospholipase D, whereas 1-butanol can reduce the generation of phosphatidate in cells by serving as a substrate for phospholipase D. These data suggest that phosphatidylinositol 3-kinase and phospholipase D may be involved in the activation of several novel protein kinases in neutrophils and that one or more of these kinases is/are involved in superoxide release.
Ding
J
J
Boston Biomedical Research Institute, MA 02114.
Badwey
J A
JA
D020001:1-Butanol; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D000440:Butanols / Q000494:pharmacology*; D006168:Guinea Pigs; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D011480:Protease Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D000440:Butanols; D011480:Protease Inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D020001:1-Butanol; D011494:Protein Kinases; D000077191:Wortmannin