Abstract
Recent studies have suggested that signaling initiated by the activation of Ag receptors and signaling activated through cytokine receptors may be regulated by a common set of inhibitory proteins. Suppressor of cytokine signaling 3 (SOCS-3), which has previously been demonstrated to inhibit cytokine signaling, is induced on TCR ligation. Overexpression of SOCS-3 can inhibit transcription driven by the IL-2 promoter in response to T cell activation. This inhibitory activity correlates with the suppression of calcineurin-dependent dephosphorylation and activation of the IL-2 promoter binding transcription factor, NFATp. Infection of primary murine T cells with a retrovirus encoding SOCS-3 blocks their IL-2 production in response to activation. Interestingly, SOCS-3 was found to coimmunoprecipitate with the catalytic subunit of calcineurin. These studies suggest that SOCS-3 may regulate T cell function as part of a negative feedback loop.
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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Calcineurin / metabolism
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Cells, Cultured
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism*
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Humans
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Interleukin-2 / genetics
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Jurkat Cells
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Mice
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Mice, Inbred C57BL
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NFATC Transcription Factors
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Nuclear Proteins*
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Phosphorylation
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Promoter Regions, Genetic
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Proteins / genetics
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Proteins / physiology*
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RNA, Messenger / biosynthesis
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Receptors, Antigen, T-Cell / metabolism
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Repressor Proteins*
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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T-Lymphocytes / immunology*
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / metabolism*
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Transcription, Genetic
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Up-Regulation
Substances
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DNA-Binding Proteins
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Interleukin-2
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NFATC Transcription Factors
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Nuclear Proteins
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Proteins
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RNA, Messenger
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Receptors, Antigen, T-Cell
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Repressor Proteins
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SOCS3 protein, human
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Socs3 protein, mouse
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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Transcription Factors
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Calcineurin