A novel conformationally restricted protein kinase C inhibitor, Ro 31‐8425, inhibits human neutrophil superoxide generation by soluble, particulate and post‐receptor stimuli
- 1 November 1991
- journal article
- Published by Wiley in FEBS Letters
- Vol. 293 (1-2) , 169-172
- https://doi.org/10.1016/0014-5793(91)81178-b
Abstract
A novel, bis-indolylmaleimide, Ro 31-8425, bearing a conformationally restricted side chain, inhibits protein kinase C isolated from rat brain and human neutrophils with a high degree of selectivity over cAMP-dependent kinase and Ca2−/calmodulin-dependent kinase. It also inhibits phorbol ester-induced intracellular events known to be mediated by protein kinase C(p47 phosphorylation in intact platelets, CD3 and CD4 down-regulation in T-cells). Ro 31-8425 inhibited superoxide generation in human neutrophils activated by both receptor stimuli (formyl-methionyl-leucylphenylalanine, opsonized zymosan. IgG and heat aggregated IgG) and post-rcceptor stimuli (1,2-dioctanoylglycerol and fluoride). The compound also blocked antigen driven, but not IL-2 induced, T-cell proliferation. These results support a central role for protein kinase C in the activation of the respiratory burst and antigen-driven T-cell proliferationKeywords
This publication has 22 references indexed in Scilit:
- Modulation of cellular processes by H7, a non-selective inhibitor of protein kinasesInflammation Research, 1991
- K252a is a potent and selective inhibitor of phosphorylase kinaseBiochemical and Biophysical Research Communications, 1990
- Phosphatidic acid and not diacylglycerol generated by phospholipase D is functionally linked to the activation of the NADPH oxidase by FMLP in human neutrophilsBiochemical and Biophysical Research Communications, 1990
- Potent selective inhibitors of protein kinase CFEBS Letters, 1989
- Studies with protein kinase C inhibitors presently available cannot elucidate the role of protein kinase C in the activation of NADPH oxidaseBiochemical and Biophysical Research Communications, 1988
- The diacylglycerol kinase inhibitor, R59022, enhances the superoxide generation from human neutrophils induced by stimulation of fMet-Leu-Phe, IgG and C3b receptorsBiochemical and Biophysical Research Communications, 1987
- K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinasesBiochemical and Biophysical Research Communications, 1986
- The protein kinase C inhibitors H-7 and H-9 fail to inhibit human neutrophil activationBiochemical and Biophysical Research Communications, 1986
- Staurosporine, a potent inhibitor of phospholipidCa++dependent protein kinaseBiochemical and Biophysical Research Communications, 1986
- Relationship between intact cell ATP levels and glucocorticoid receptor-binding capacity in the AtT-20 cellBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1985