Protein kinase C θ affects Ca2+ mobilization and NFAT cell activation in primary mouse T cells
Protein kinase C θ affects Ca2+ mobilization and NFAT cell activation in primary mouse T cells
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DOI：
10.1084/jem.20020234
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发表时间：
2003-06-02
影响因子：
15.3
通讯作者：
Baier, G
中科院分区：
文献类型：
--
作者：
Pfeifhofer, C;Kofler, K;Baier, G
蛋白激酶C（PKC）θ是免疫突触的一个既定组成部分，并参与AP-1和NF-κ B的控制。为了研究PKC θ的生理功能，我们使用基因靶向在小鼠中产生PKC θ无效等位基因。一致的是，白细胞介素2的生产和T细胞增殖反应强烈减少PKC θ缺陷的T细胞。然而，令人惊讶的是，我们证明了在CD 3/CD 28接合后，PKC θ的缺乏主要消除了NFAT的反式激活。相反，NF-κ B活化仅部分减少。这种NFAT反式激活缺陷似乎是继发于减少肌醇1，4，5-三磷酸生成和细胞内Ca（2+）动员。我们的研究结果表明，PKC θ在T细胞受体诱导的NFAT激活中起着关键和非冗余的作用。
Protein kinase C (PKC)theta is an established component of the immunological synapse and has been implicated in the control of AP-1 and NF-kappaB. To study the physiological function of PKCtheta, we used gene targeting to generate a PKCtheta null allele in mice. Consistently, interleukin 2 production and T cell proliferative responses were strongly reduced in PKCtheta-deficient T cells. Surprisingly, however, we demonstrate that after CD3/CD28 engagement, deficiency of PKCtheta primarily abrogates NFAT transactivation. In contrast, NF-kappaB activation was only partially reduced. This NFAT transactivation defect appears to be secondary to reduced inositol 1,4,5-trisphosphate generation and intracellular Ca(2+) mobilization. Our finding suggests that PKCtheta plays a critical and nonredundant role in T cell receptor-induced NFAT activation.