Ye Keqiang
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Cell Biochem. 2005 Oct 15;96(3):463-72. doi: 10.1002/jcb.20549.
PI 3-kinase enhancer (PIKE) is a nuclear GTPase that enhances PI 3-kinase (PI3K) activity. Nerve growth factor (NGF) treatment leads to PIKE activation by triggering the nuclear translocation of PLC-gamma1, which acts as a physiological guanine nucleotide exchange factor (GEF) for PIKE. PI3K occurs in the nuclei of a broad range of cell types, and various stimuli elicit PI3K nuclear translocation. While cytoplasmic PI3K has been well characterized, little is known about the biological function of nuclear PI3K. Surprisingly, nuclei from 30 min NGF-treated PC12 cells are resistant to DNA fragmentation initiated by the activated cell-free apoptosome, and both PIKE and nuclear PI3K are sufficient and necessary for this effect. Moreover, pretreatment of the control nucleus with PI(3,4,5)P3 alone mimics the anti-apoptotic activity of NGF by selectively preventing apoptosis, for which nuclear Akt is required but not sufficient. Recently, a nuclear PI(3,4,5)P3 receptor, nucleophosmin/B23, has been identified from NGF-treated PC12 nuclear extract. PI(3,4,5)P3/B23 complex mediates the anti-apoptotic effects of NGF by inhibiting DNA fragmentation activity of caspase-activated DNase (CAD). Thus, PI(3,4,5)P3/B23 complex and nuclear Akt effectors might coordinately mediate PIKE/nuclear PI3K signaling in promoting cell survival by NGF.
PI3激酶增强子（PIKE）是一种核鸟苷三磷酸酶，可增强PI3激酶（PI3K）的活性。神经生长因子（NGF）处理通过触发PLC-γ1的核转位来激活PIKE，PLC-γ1作为PIKE的生理性鸟嘌呤核苷酸交换因子（GEF）。PI3K存在于多种细胞类型的细胞核中，各种刺激均可引发PI3K的核转位。虽然细胞质PI3K已得到充分表征，但对于核PI3K的生物学功能知之甚少。令人惊讶的是，来自经30分钟NGF处理的PC12细胞的细胞核对由活化的无细胞凋亡小体引发的DNA片段化具有抗性，并且PIKE和核PI3K对于这种效应都是充分且必要的。此外，仅用PI(3,4,5)P3预处理对照细胞核可通过选择性地防止细胞凋亡来模拟NGF的抗凋亡活性，而这需要核Akt但不充分。最近，已从NGF处理的PC12核提取物中鉴定出一种核PI(3,4,5)P3受体，核仁磷酸蛋白/B23。PI(3,4,5)P3/B23复合物通过抑制半胱天冬酶激活的脱氧核糖核酸酶（CAD）的DNA片段化活性来介导NGF的抗凋亡作用。因此，PI(3,4,5)P3/B23复合物和核Akt效应器可能在促进NGF介导的细胞存活中协同介导PIKE/核PI3K信号传导。
