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首页> 外文期刊>Genes to cells : >Protein phosphatase 1 is involved in IL-2-induced IL-5 and IL-13 expression in human T cells
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Protein phosphatase 1 is involved in IL-2-induced IL-5 and IL-13 expression in human T cells

机译：蛋白磷酸酶1参与IL-2诱导的人类T细胞中IL-5和IL-13的表达

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摘要

IL-2 plays an important role in immunological and other biological functions. This cytokine directly induces the production of several cytokines, such as IL-5 and IL-13. The mechanisms of IL-2-mediated cytokine synthesis are mostly unclear; however, the involvement of IL-2 receptor (IL-2R)beta has been suggested. In this study, the signaling molecule downstream of IL-2R beta was investigated, employing a proteomic approach. Full-length IL-2R beta and its mutant in which the intracellular component was truncated were introduced in an IL-2Ra- and IL-2R?-stably transfected T cell hybridoma, S1. The differential phosphorylation profiles of protein tyrosine residues in these cells upon IL-2 stimulation were examined by two-dimensional gel electrophoresis. The candidate phosphoproteins of interest were re-covered, in-gel digested and mass spectrometry fingerprinted. Among proteins specifically phosphorylated in full-length IL-2R beta-expressing cells in response to IL-2 stimulation, protein phosphatase (PP)1 beta and FK506-binding protein 4 were identified. Particularly, PP1 beta augmented IL-5 and IL-13 expression stimulated by IL-2 but not by anti-CD3 antibody in human peripheral CD4+ T cells upon ectopic expression. IL-2-induced cytokine expression was suppressed by overexpression of PP1 regulatory subunit 2. A PP1 inhibitor, tautomycin, but not a PP2A inhibitor, okadaic acid, also inhibited the IL-2R-mediated responses. It was conclusively shown that PP1 is crucially involved in IL-2-mediated IL-5 and IL-13 synthesis in human T cells.
机译：IL-2在免疫和其他生物学功能中起重要作用。该细胞因子直接诱导几种细胞因子的产生，例如IL-5和IL-13。 IL-2介导的细胞因子合成的机制大多尚不清楚。然而，已经提出了IL-2受体（IL-2R）β的参与。在这项研究中，采用蛋白质组学方法研究了IL-2R beta下游的信号分子。将全长的IL-2Rβ及其突变体（其中的细胞内成分被截短）引入稳定的IL-2Ra和IL-2Rα转染的T细胞杂交瘤S1中。通过二维凝胶电泳检查了IL-2刺激后这些细胞中蛋白质酪氨酸残基的差异磷酸化谱。感兴趣的候选磷酸蛋白被重新回收，在凝胶中被消化并被质谱指纹图谱。在响应IL-2刺激而在全长IL-2R beta表达细胞中特异性磷酸化的蛋白中，鉴定出了蛋白磷酸酶（PP）1 beta和FK506结合蛋白4。特别地，异位表达后，PP1β增强了人外周CD4 + T细胞中IL-2刺激的IL-5和IL-13表达，但不受抗CD3抗体刺激。 PP1-2调节亚基2的过表达抑制了IL-2诱导的细胞因子的表达。PP1抑制剂互变霉素，而不是PP2A抑制剂冈田酸，也抑制了IL-2R介导的应答。最终表明，PP1至关重要地参与了人类T细胞中IL-2介导的IL-5和IL-13的合成。

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