Cutting edge: Suppressor of cytokine signaling 3 inhibits activation of NFATp.
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.
Mesh Terms:
Animals, Calcineurin, Cells, Cultured, DNA-Binding Proteins, Humans, Interleukin-2, Jurkat Cells, Mice, Mice, Inbred C57BL, NFATC Transcription Factors, Nuclear Proteins, Phosphorylation, Promoter Regions, Genetic, Proteins, RNA, Messenger, Receptors, Antigen, T-Cell, Repressor Proteins, Suppressor of Cytokine Signaling Proteins, T-Lymphocytes, Transcription Factors, Transcription, Genetic, Up-Regulation
Animals, Calcineurin, Cells, Cultured, DNA-Binding Proteins, Humans, Interleukin-2, Jurkat Cells, Mice, Mice, Inbred C57BL, NFATC Transcription Factors, Nuclear Proteins, Phosphorylation, Promoter Regions, Genetic, Proteins, RNA, Messenger, Receptors, Antigen, T-Cell, Repressor Proteins, Suppressor of Cytokine Signaling Proteins, T-Lymphocytes, Transcription Factors, Transcription, Genetic, Up-Regulation
J. Immunol.
Date: May. 01, 2002
PubMed ID: 11970967
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