Abstract
A region of the interleukin-2 (IL-2) promoter known as the RE/AP element is activated in concert by signals that originate from the T cell antigen receptor and the CD28 coreceptor. We show here that the serine-threonine kinase Akt can provide a costimulatory signal for RE/AP activation that is indistinguishable from the signal provided by CD28. This includes the ability of Akt, like antibodies to CD28, to synergize with protein kinase C theta (PKC-theta) in the induction of RE/AP. Retrovirus-mediated expression of activated Akt in primary T cells from CD28-deficient mice is capable of selectively restoring production of IL-2 and interferon gamma, but not IL-4 or IL-5. Our results provide evidence that CD28 costimulation of different cytokines is mediated by discrete signaling pathways, one of which includes Akt.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD28 Antigens / metabolism*
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Cell Line
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Cytokines / metabolism
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Humans
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Interferon-gamma / biosynthesis*
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Interleukin-2 / biosynthesis*
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Transgenic
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Models, Biological
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphorylation
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Protein-Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Receptors, Antigen, T-Cell / metabolism
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Signal Transduction
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T-Lymphocytes / immunology
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Th2 Cells / immunology
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Up-Regulation
Substances
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CD28 Antigens
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Cytokines
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Interleukin-2
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Proto-Oncogene Proteins
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Receptors, Antigen, T-Cell
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Interferon-gamma
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Phosphatidylinositol 3-Kinases
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AKT1 protein, human
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Protein-Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt