Abstract
Stimulation of T cells through their antigen receptors (TCRs) causes a transient increase in the intracellular concentration of cyclic AMP (cAMP). However, sustained high levels of cAMP inhibit T-cell responses, suggesting that TCR signaling is coordinated with the activation of cyclic nucleotide phosphodiesterases (PDEs). The molecular basis of such a pathway is unknown. Here we show that TCR-dependent signaling activates PDE4B2 and that this enhances interleukin-2 production. Such an effect requires the regulatory N terminus of PDE4B2 and correlates with partitioning within lipid rafts, early targeting of this PDE to the immunological synapse, and subsequent accumulation in the antipodal pole of the T cell as activation proceeds.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / chemistry
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3',5'-Cyclic-AMP Phosphodiesterases / genetics
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3',5'-Cyclic-AMP Phosphodiesterases / metabolism*
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Cell Compartmentation
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Enzyme Activation
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Humans
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In Vitro Techniques
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Interleukin-2 / biosynthesis
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Jurkat Cells
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Lymphocyte Activation
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Membrane Microdomains / enzymology
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Protein Structure, Tertiary
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Receptors, Antigen, T-Cell / metabolism
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sequence Deletion
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Signal Transduction
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T-Lymphocytes / enzymology*
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T-Lymphocytes / immunology*
Substances
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Interleukin-2
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 4