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.
Department of Molecular Immunology, Institute for Biology III, University of Freiburg and Max Planck Institute for Immunobiology, Stübeweg 51, 79108 Freiburg, Germany.
Eva
E
Lessmann
Michael
M
Leitges
Michael
M
Huber
D000818:Animals; D015550:Cell Degranulation / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D020935:MAP Kinase Signaling System; D008297:Male; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051744:Protein Kinase C-epsilon / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology; D015398:Signal Transduction
C501470:FcRI protein, mouse; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D018664:Interleukin-12; D007073:Immunoglobulin E; D019009:Proto-Oncogene Proteins c-kit; D051744:Protein Kinase C-epsilon