Akt provides the CD28 costimulatory signal for up-regulation of IL-2 and IFN-γ but not TH2 cytokines
Akt provides the CD28 costimulatory signal for up-regulation of IL-2 and IFN-γ but not TH2 cytokines
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DOI：
10.1038/83144
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发表时间：
2001-01-01
影响因子：
30.5
通讯作者：
Weiss, A
中科院分区：
文献类型：
--
作者：
Kane, LP;Andres, PG;Weiss, A
白细胞介素-2 （IL-2）启动子的RE/AP元件区域被来自T细胞抗原受体和CD28辅助受体的信号协同激活。我们在这里表明，丝氨酸-苏氨酸激酶Akt可以为RE/AP激活提供一个与CD28提供的信号难以区分的共刺激信号。这包括Akt与CD28抗体一样，在诱导RE/AP过程中与蛋白激酶C-theta （PKC-theta）协同的能力。逆转录病毒介导的活化Akt在cd28缺陷小鼠原代T细胞中的表达能够选择性地恢复IL-2和干扰素γ的产生，但不能恢复IL-4或IL-5的产生。我们的研究结果证明，不同细胞因子的CD28共刺激是由离散的信号通路介导的，其中一个信号通路包括Akt。
A region of the interleukin-2 (IL-2) promoter known as the RE/AP element is activated in concert by signals that originate from the T cell antigen receptor and the CD28 coreceptor. We show here that the serine-threonine kinase Akt can provide a costimulatory signal for RE/AP activation that is indistinguishable from the signal provided by CD28. This includes the ability of Akt, like antibodies to CD28, to synergize with protein kinase C theta (PKC-theta) in the induction of RE/AP. Retrovirus-mediated expression of activated Akt in primary T cells from CD28-deficient mice is capable of selectively restoring production of IL-2 and interferon gamma, but not IL-4 or IL-5. Our results provide evidence that CD28 costimulation of different cytokines is mediated by discrete signaling pathways, one of which includes Akt.