Different agonists recruit different stromal interaction molecule proteins to support cytoplasmic Ca2+ oscillations and gene expression

Different agonists recruit different stromal interaction molecule proteins to support cytoplasmic Ca2+ oscillations and gene expression
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DOI:
10.1073/pnas.1201204109
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发表时间:
2012-05-01
影响因子:
11.1
通讯作者:
Parekh, Anant B.
Parekh, Anant B.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kar, Pulak;Bakowski, Daniel;Parekh, Anant B.

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用生理浓度的钙动员激动剂刺激细胞通常导致产生重复的胞质Ca 2+振荡。虽然振荡是由再生Ca 2+释放引起的,但它们是由通过Ca 2+释放激活的Ca 2+(CRAC)通道的钙库操作的Ca 2+进入维持的。在这里,我们表明,在大鼠嗜碱性白血病(RBL)-1细胞,大幅度的钙振荡,CRAC通道活性,和下游的激活T细胞(NFAT)的钙依赖性核因子驱动的基因表达的半胱氨酰白三烯I型受体的刺激都是专门维持内质网钙离子传感器基质相互作用分子(STIM)1。然而,刺激酪氨酸激酶偶联的FCRRI受体诱发钙振荡和NFAT依赖的基因表达,通过招募的STIM 2和STIM 1。我们得出结论,不同的激动剂激活不同的STIM蛋白,以维持Ca 2+信号和下游反应。
Stimulation of cells with physiological concentrations of calcium-mobilizing agonists often results in the generation of repetitive cytoplasmic Ca2+ oscillations. Although oscillations arise from regenerative Ca2+ release, they are sustained by store-operated Ca2+ entry through Ca2+ release-activated Ca2+ (CRAC) channels. Here, we show that following stimulation of cysteinyl leukotriene type I receptors in rat basophilic leukemia (RBL)-1 cells, large amplitude Ca2+ oscillations, CRAC channel activity, and downstream Ca2+-dependent nuclear factor of activated T cells (NFAT)-driven gene expression are all exclusively maintained by the endoplasmic reticulum Ca2+ sensor stromal interaction molecule (STIM) 1. However, stimulation of tyrosine kinase-coupled FC epsilon RI receptors evoked Ca2+ oscillations and NFAT-dependent gene expression through recruitment of both STIM2 and STIM1. We conclude that different agonists activate different STIM proteins to sustain Ca2+ signals and downstream responses.