Kane L P, Andres P G, Howland K C, Abbas A K, Weiss A
Department of Medicine, University of California, San Francisco, CA 94143, USA.
Nat Immunol. 2001 Jan;2(1):37-44. doi: 10.1038/83144.
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.
白细胞介素-2(IL-2)启动子中有一个被称为RE/AP元件的区域,它会被源自T细胞抗原受体和CD28共受体的信号协同激活。我们在此表明,丝氨酸-苏氨酸激酶Akt能够为RE/AP激活提供共刺激信号,该信号与CD28提供的信号无法区分。这包括Akt与抗CD28抗体一样,在诱导RE/AP时与蛋白激酶Cθ(PKC-θ)协同作用的能力。逆转录病毒介导的活化Akt在来自CD28缺陷小鼠的原代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。我们的结果提供了证据,表明CD28对不同细胞因子的共刺激是由离散的信号通路介导的,其中一条通路包括Akt。