Regulation of interleukin‐2 responses by phosphatidic acid
Regulation of interleukin‐2 responses by phosphatidic acid
复制标题
磷脂酸调节白介素-2 反应
DOI：
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发表时间：
1992
影响因子：
5.4
通讯作者：
Centro de Biología Molecular
中科院分区：
文献类型：
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作者：
E. Cano;M. A. Muiioz;M. Fresno;Centro de Biología Molecular
白介素2(IL-2)通过调节T淋巴细胞的增殖和分化，在免疫系统中发挥核心作用。然而，通过IL-2受体进行信号转导的分子机制却知之甚少。我们利用克隆的T淋巴细胞研究了磷脂酸(PA)在IL-2信号转导中的作用。IL-2刺激预先标记了[~3H]棕榈酸的静息CTLL-2细胞一过性增加PA浓度。这种作用早在加入IL-2后1min就可检测到，并在5min时达到高峰。IL-2类似地增加了完整的CTLL-2细胞中磷脂酶D的活性，正如磷脂酰乙醇的产生所推断的那样。相反，IL-2不影响[~3H]棕榈酸标记的二酰甘油水平。此外，在T细胞中加入几种天然或合成的PA可以模拟IL-2的活性。因此，PA能诱导CTLL-2细胞DNA合成，但仅为IL-2作用的10%~20%。PA与低剂量IL-2有协同作用。PA还能诱导CTLL-2细胞c-myc RNA转录和细胞膜上IL-2受体(CD25)的表达，其作用强度与饱和剂量IL-2相当。外源性磷脂酶D而不是磷脂酰肌醇特异性磷脂酶C的加入也复制了上述IL-2或PA效应，这一事实进一步支持了这一假设。综上所述，我们的结果提示磷脂酶D的激活和PA的形成是IL-2活性的第二信使。
Interleukin‐2 (IL‐2) plays a central role in the immune system by regulating the proliferation and differentiation of T lymphocytes. However, the molecular mechanism of the signal transduction through the IL‐2 receptor is poorly understood. We have studied the role of phosphatidic acid (PA) on IL‐2 signal transduction using cloned T lymphocytes. IL‐2 stimulated a transient increase in the PA concentration in resting CTLL‐2 cells prelabeled with [3H]palmitic acid. This effect was detected as early as 1 min after IL‐2 addition and peaked at 5 min. IL‐2 similarly increased phospholipase D activity in intact CTLL‐2 cells, as inferred by phosphatidylethanol production. By contrast, IL‐2 did not affect [3H]palmitic acid‐labeled diacylglycerol levels. Furthermore, exogenous addition of several natural or synthetic PA to T cells mimicked IL‐2 activity. Thus, PA were able to induce DNA synthesis on CTLL‐2 cells, although this effect was only 10%–20% of that observed with IL‐2. PA showed a synergistic effect with low doses of IL‐2. In addition, PA was able to induce c‐myc RNA transcription in CTLL‐2 cells as well as IL‐2 receptor (CD25) expression on the cell membrane with equal potency as saturating doses of IL‐2. It is likely that IL‐2‐induced PA accumulation is a consequence of phospholipase D activation. This hypothesis is further supported by the fact that the addition of exogenous phospholipase D but not phosphatidylinositol‐specific phospholipase C also reproduced the IL‐2 or PA effects mentioned above. In summary, our results suggest a role of phospholipase D activation and PA formation as second messengers of IL‐2 activity.
蛋白激酶 C 激活解离和 sn-1,2-二酰基甘油形成。
DOI：
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发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Leach,KL;Ruff,VA;Wright,TM;Pessin,MS;Raben,DM
通讯作者：
Raben,DM
影响因子：
56.9
作者：
CANTRELL, DA;SMITH, KA
通讯作者：
SMITH, KA
PMA 单独诱导一些鼠 T 细胞克隆的增殖，但不诱导其他细胞克隆的增殖。
DOI：
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发表时间：
1986
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kim,DK;Otten,G;Moldwin,RL;Dunn,DE;Nau,GJ;Fitch,FW
通讯作者：
Fitch,FW