Recently, the expression of the mRNA for the proto-oncogene c-fos following activation of the high-affinity receptor for immunoglobulin E in rodent mast cells has been reported. In the present study we investigated different biochemical events that may play a role in signal transduction pathways culminating in the expression of c-fos mRNA in rat basophilic leukaemia cells. Similar to IgE-mediated cell degranulation we demonstrated inhibition of the c-fos signal in the absence of calcium and after preincubation of cells with the protein tyrosine kinase inhibitor genistein. Activation of RBL-2H3 cells by short term PMA treatment failed to induce cell degranulation or expression of mRNA for c-fos. Depletion of protein kinase C by PMA pre-treatment resulted in substantial inhibition of the c-fos signal. In contrast to IgE-mediated cell degranulation, expression of mRNA for c-fos was not dependent on continued receptor aggregation. In addition, we demonstrate that c-fos mRNA expression is not restricted to FcϵRI activation but can be induced by a variety of IgE independent mechanisms including calcium influx by ionophore A 23187 and stimulation of G proteins.
