Dupuis G, Martel J, Bastin B, Dion J, Payet M D
Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Cell Immunol. 1993 Jan;146(1):38-51. doi: 10.1006/cimm.1993.1004.
We have used two disruptors of the cytoskeleton microtubular network (colchicine and vinblastine) to investigate the role of microtubules in Phaseolus vulgaris phytohemagglutinin (PHA) signal transduction in Jurkat T cells. Both drugs decreased but did not abolish the PHA-dependent Ca2+ response of Jurkat cells. Neither colchicine nor vinblastine had any major effects on the PHA-dependent turnover of the mono-, di-, tri-, and tetra-substituted phosphorylated derivatives of D-myo-inositol or the cellular distribution of protein kinase C (PKC) activity. However, both microtubule disruptors increased interleukin-2 (IL-2) production. Whereas vinblastine enhanced IL-2 production approximately twofold at all the concentrations tested (0.1, 1.0, and 10 microM), colchicine did so only at a 10 microM concentration. When a combination of PHA and 12-O-tetradecanoyl-13-O-acetyl phorbol (TPA) was used, a small increase in IL-2 production was observed only in the presence of vinblastine (10 microM). In contrast to recent reports that microfilaments may be involved in the regulation of signal transduction, our data suggest that this is not the case for microtubules in PHA-dependent signal transduction in Jurkat T cells.
我们使用了两种细胞骨架微管网络破坏剂(秋水仙碱和长春花碱)来研究微管在Jurkat T细胞中菜豆植物血凝素(PHA)信号转导中的作用。两种药物均降低了Jurkat细胞对PHA依赖性的Ca2+反应,但并未完全消除。秋水仙碱和长春花碱对D-肌醇单、二、三、四取代磷酸化衍生物的PHA依赖性周转或蛋白激酶C(PKC)活性的细胞分布均无任何重大影响。然而,两种微管破坏剂均增加了白细胞介素-2(IL-2)的产生。长春花碱在所有测试浓度(0.1、1.0和10 microM)下均使IL-2产生增加约两倍,而秋水仙碱仅在10 microM浓度下才会如此。当使用PHA和12-O-十四烷酰-13-O-乙酰佛波醇(TPA)的组合时,仅在存在长春花碱(10 microM)的情况下才观察到IL-2产生略有增加。与最近关于微丝可能参与信号转导调节的报道相反,我们的数据表明在Jurkat T细胞中PHA依赖性信号转导中微管并非如此。