Brennan P, Babbage J W, Burgering B M, Groner B, Reif K, Cantrell D A
Lymphocyte Activation Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Immunity. 1997 Nov;7(5):679-89. doi: 10.1016/s1074-7613(00)80388-x.
Cell cycle progression initiated by interleukin-2 (IL-2) in T cells is critical for lymphoproliferation and an immune response. Phosphatidyl inositol 3-kinase (PI3K) is activated by IL-2. However, nuclear targets for PI3K are not known. Here we identify the cell cycle regulator E2F as an IL-2 target in T lymphocytes and PI3K as the critical signaling pathway. We eliminate both Stat5 and Raf/MEK pathways from E2F regulation. Protein kinase B (PKB) is activated by IL-2 via PI3K. The expression of an active PKB is sufficient to induce E2F activity. Inhibition of PI3K inhibits phosphorylation of Rb, induction of cyclin D3, and degradation of p27kip1. These results establish a crucial PI3K/PKB-mediated link between the IL-2 teceptor and the cell cycle machinery.
白细胞介素-2（IL-2）在T细胞中启动的细胞周期进程对淋巴细胞增殖和免疫反应至关重要。磷脂酰肌醇3激酶（PI3K）被IL-2激活。然而，PI3K的核靶点尚不清楚。在此，我们确定细胞周期调节因子E2F为T淋巴细胞中的IL-2靶点，PI3K为关键信号通路。我们从E2F调节中消除了Stat5和Raf/MEK通路。蛋白激酶B（PKB）通过PI3K被IL-2激活。活性PKB的表达足以诱导E2F活性。抑制PI3K可抑制Rb的磷酸化、细胞周期蛋白D3的诱导以及p27kip1的降解。这些结果在IL-2受体与细胞周期机制之间建立了关键的PI3K/PKB介导的联系。
