Protein kinase C regulation of the receptor-coupled calcium signal in histamine-secreting rat basophilic leukaemia cells.
It has been proposed that protein kinase C mediates cellular responses evoked by external stimuli, leading to alterations in internal free calcium concentrations. We have shown previously that histamine-secreting rat basophilic leukaemia cells (RBL-2H3), which degranulate on aggregation of the receptors for immunoglobulin IgE, contain a Ca2+- and phospholipid-dependent protein kinase (kinase C). The partially purified enzyme is activated directly by the tumour-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). In intact RBL cells, TPA potentiates histamine release induced by the Ca2+-ionophore A23187 (similar to the synergy reported for platelets, neutrophils and rat peritoneal mast cells). Although TPA at concentrations below 15 nM synergizes with the antigen, higher TPA concentrations inhibit secretion. This selective inhibition suggested that kinase C is involved in both the activation and termination of the secretory process. To examine this possibility, we have determined the effect of TPA on changes in free cytosolic Ca2+ concentration during antigen-induced release. We report here that TPA completely blocks the increase in Ca2+ concentration induced by antigen. Our results strongly suggest that protein kinase C is involved in the regulation of receptor-dependent Ca2+ signalling.
Sagi-Eisenberg
R
R
Lieman
H
H
Pecht
I
I
D001491:Basophils / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D006636:Histamine Release; D007473:Ion Channels / Q000502:physiology; D007938:Leukemia / Q000503:physiopathology; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D011946:Receptors, Antigen / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007473:Ion Channels; D010704:Phorbols; D011946:Receptors, Antigen; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium