SELECTIVE-INHIBITION BY H7 AND STAUROSPORIN OF PHORBOL ESTER RESPONSES IN U-937 CELLS

The kinase inhibitors H7 and staurosporin dose-dependently stimulate a dhesion of U-937 cells to plastic but fail to inhibit the CD11b/CD18-d ependent adhesion of U-937 cells induced by phorbol ester. The protein kinase C activity of U-937 cells, measured as phorbol ester-stimulate d phosphorylation of pepepsilon in streptolysin-0 permeabilized cells, is strongly inhibited by the kinase inhibitors. H7 and staurosporin e fficiently overcome the inhibitory effect of phorbol-12,13-dibutyrate (PDBu) on leukotriene D4-induced increase in intracellular Ca2+. The r esults suggest that U-937 cell adhesion may be controlled by a protein kinase C isoform not sensitive to the inhibitors. In addition, the da ta indicate that selective pharmacological interference with different protein kinase C-mediated processes is achievable.