Inhibition of degranulation and interleukin-6 production in mast cells derived from mice deficient in protein kinase C beta

The antigen-mediated activation of mast cells by means of IgE antibodies bo und to the cell surface leads to direct interactions between Fc epsilon RI receptor cytoplasmic domains and various intracellular proteins, These inte ractions initiate diverse signal-transduction pathways, and the activation of these pathways results in the immediate release of proinflammatory agent s. A delayed response also occurs and includes the release of various cytok ines, It is clear that the activation of kinases is a requirement for the e xocytosis observed in mast cells. In addition to the tyrosine phosphorylati on of the affected system by soluble tyrosine kinases, activity of protein kinase C (PKC) results in serine or threonine phosphorylation of multiple p rotein substrates, In this study, we found that mast cells derived from PKC beta-deficient mice produce less interleukin 6 in response to IgE-Ag. The inhibition of exocytosis in the PKC beta-deficient mast cells occurred whet her the stimuli were due to the aggregation of the mast cell surface Fc eps ilon RI or to the calcium ionophore, ionomycin. However, no significant cha nges were observed in the proliferative response of the mast cells to inter leukin 3 (IL-3) or in their apoptotic rate after IL-3 depletion. (C) 2000 b y The American Society of Hematology.