Protein kinase Cepsilon is dispensable for TCR/CD3-signaling.
PKCepsilon has been strongly linked to cell activation and proliferation in many cell types, including leukemic T-cell lines. In particularly, an essential role of PKCepsilon has been established in the IKK-beta/I-kappaB/NF-kappaB transactivation cascade. To study the physiological function of PKCepsilon in primary T-cells, we used our newly established PKCepsilon null mice. Unexpectedly, however, we did not reveal any defect in the development and function of CD3+ T-cells. Proliferative responses as well as IL-2 cytokine secretion of PKCepsilon-deficient T-cells induced by allogenic MHC, plate-bound anti-CD3 antibodies (with or without anti-CD28 costimulation), or mitogenic stimuli such as phorbol ester and Ca2+ ionophore were comparable with wild-type controls. Consistently, after CD3/CD28 engagement, deficiency of PKCepsilon did not impair NF-kappaB transactivation as well as CD25, CD44 and CD69 induction. Thus, PKCepsilon-deficient T-cells had similar physiological thresholds for activation in vitro. This finding suggests that PKCepsilon plays a redundant role in TCR-induced regulation of T-cell proliferation.
Gruber
Thomas
T
Department for Medical Biology and Human Genetics, Medical University of Innsbruck, Schoepfstrasse 41, A-6020 Innsbruck, Austria.
Thuille
Nikolaus
N
Hermann-Kleiter
Natascha
N
Leitges
Michael
M
Baier
Gottfried
G
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000502:physiology; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D051744:Protein Kinase C-epsilon; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D015533:Transcriptional Activation / Q000235:genetics
D015703:Antigens, CD; D007376:Interleukin-2; D016328:NF-kappa B; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C497256:Prkce protein, mouse; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon