A redundant role for PKC-epsilon in mast cell signaling and effector function.

Protein kinase (PK) C-epsilon is strongly expressed in mast cells (MCs) and activated in response to antigen-mediated high-affinity receptor for IgE (Fc epsilonR1) engagement. A critical role of PKC-epsilon in antigen-triggered activation of various signaling pathways was observed in basophilic leukemia cells. To study the function of PKC-epsilon in MCs differentiated in vitro from murine bone marrow, we used our established PKC-epsilon null mice. Unexpectedly, we did not reveal any difference in antigen-induced activation of many central signaling molecules (PKB, mitogen-activated protein kinase, p38, Jun-N-terminal kinase, phospholipase C-gamma1, Bruton's tyrosine kinase, PKD, Fos and PKC-delta) in time-course as well as dose-response studies between PKC-epsilon-deficient and wild-type MCs. In correlation, antigen-triggered degranulation, release of arachidonic acid and secretion of IL-6 were unaltered by the loss of PKC-epsilon. Furthermore, stimulation of MCs via different receptor systems [Steel factor receptor (c-kit) and toll-like receptor 4] did not lead to differences in the measured responses between both cell types. These results strongly suggest that PKC-epsilon plays a redundant role in MCs stimulated by antigen as well as other well-known MC stimuli.