Inhibition of degranulation and interleukin-6 production in mast cells derived from mice deficient in protein kinase Cbeta.
The antigen-mediated activation of mast cells by means of IgE antibodies bound to the cell surface leads to direct interactions between FcepsilonRI receptor cytoplasmic domains and various intracellular proteins. These interactions initiate diverse signal-transduction pathways, and the activation of these pathways results in the immediate release of proinflammatory agents. A delayed response also occurs and includes the release of various cytokines. It is clear that the activation of kinases is a requirement for the exocytosis observed in mast cells. In addition to the tyrosine phosphorylation of the affected system by soluble tyrosine kinases, activity of protein kinase C (PKC) results in serine or threonine phosphorylation of multiple protein substrates. In this study, we found that mast cells derived from PKCbeta-deficient mice produce less interleukin 6 in response to IgE-Ag. The inhibition of exocytosis in the PKCbeta-deficient mast cells occurred whether the stimuli were due to the aggregation of the mast cell surface FcepsilonRI or to the calcium ionophore, ionomycin. However, no significant changes were observed in the proliferative response of the mast cells to interleukin 3 (IL-3) or in their apoptotic rate after IL-3 depletion. (Blood. 2000;95:1752-1757)
Nechushtan
H
H
Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Leitges
M
M
Cohen
C
C
Kay
G
G
Razin
E
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015549:Basophil Degranulation Test; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D007073:Immunoglobulin E / Q000276:immunology*; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016685:Mitomycin / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D064546:Protein Kinase C beta; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
D007377:Interleukin-3; D015850:Interleukin-6; D007527:Isoenzymes; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E; D016685:Mitomycin; D015759:Ionomycin; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D002118:Calcium