Abstract
PKCbeta has been established to be essential in B cell receptor (BCR) signaling. Additionally, a critical role of PKCbeta in TCR/CD28-stimulated regulation of IL-2 gene transcription but also exocytotic IL-2 secretion was observed in leukemic T cell lines. To now study the physiological function of PKCbeta in primary CD3(+) T cells, we used our established PKCbeta null mice. Unexpectantly, we did not reveal any defect in the development and function of T cells. Proliferative responses as well as IL-2 cytokine secretion of PKCbeta-deficient CD3(+) 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 Ca(2+) ionophore were comparable with wild-type controls. Thus, PKCbeta-deficient T cells had similar physiological thresholds for activation in vitro. These findings suggest that PKCbeta plays a redundant role in TCR-induced regulation of IL-2 cytokine production and T cell proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD28 Antigens / immunology
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Cell Division
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Genes, Reporter
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Humans
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Ionomycin / pharmacology
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Ionophores / pharmacology
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Isoenzymes / genetics
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Isoenzymes / physiology
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Jurkat Cells
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Luciferases / biosynthesis
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Luciferases / genetics
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Lymphocyte Activation
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Muromonab-CD3 / pharmacology
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Phorbol 12,13-Dibutyrate / pharmacology
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Promoter Regions, Genetic / genetics
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Protein Kinase C / deficiency
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Protein Kinase C / genetics
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Protein Kinase C / physiology*
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Protein Kinase C-theta
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Receptors, Antigen, T-Cell / physiology*
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Recombinant Fusion Proteins / physiology
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Signal Transduction
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T-Lymphocytes / enzymology*
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T-Lymphocytes / immunology
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Transfection
Substances
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CD28 Antigens
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Interleukin-2
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Ionophores
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Isoenzymes
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Muromonab-CD3
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
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Phorbol 12,13-Dibutyrate
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Ionomycin
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Luciferases
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PRKCQ protein, human
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Prkcq protein, mouse
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Protein Kinase C
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Protein Kinase C-theta