Regulation of T-cell activation by phosphodiesterase 4B2 requires its dynamic redistribution during immunological synapse formation
Regulation of T-cell activation by phosphodiesterase 4B2 requires its dynamic redistribution during immunological synapse formation
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DOI：
10.1128/mcb.23.22.8042-8057.2003
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发表时间：
2003-11-01
影响因子：
5.3
通讯作者：
Madrenas, J
中科院分区：
文献类型：
--
作者：
Arp, J;Kirchhof, MG;Madrenas, J
通过T细胞的抗原受体（TCR）刺激T细胞引起环AMP（cAMP）的细胞内浓度的瞬时增加。然而，持续高水平的cAMP抑制T细胞应答，表明TCR信号传导与环核苷酸磷酸二酯酶（PDE）的活化相协调。这种途径的分子基础是未知的。在这里，我们表明，TCR依赖性信号激活PDE 4 B2，这增强了白细胞介素-2的生产。这种作用需要调节PDE 4 B2的N末端，并且与脂筏内的分配、该PDE对免疫突触的早期靶向以及随后随着活化进行在T细胞的对极中的积累相关。
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.