REQUIREMENT FOR PHOSPHATIDYLINOSITOL-3 KINASE IN THE PREVENTION OF APOPTOSIS BY NERVE GROWTH-FACTOR
REQUIREMENT FOR PHOSPHATIDYLINOSITOL-3 KINASE IN THE PREVENTION OF APOPTOSIS BY NERVE GROWTH-FACTOR
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DOI：
10.1126/science.7701324
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发表时间：
1995-03-31
期刊：
影响因子：
56.9
通讯作者：
COOPER, GM
中科院分区：
文献类型：
--
作者：
YAO, RJ;COOPER, GM
神经生长因子（NGF）通过与Trk受体蛋白酪氨酸激酶结合诱导神经元分化和存活。虽然Pas是大鼠嗜铬细胞瘤PC-12细胞在无血清培养基中分化所必需的，但它不是ngf介导的大鼠嗜铬细胞瘤PC-12细胞存活所必需的。然而，NGF阻止凋亡（程序性细胞死亡）的能力被wortmannin或LY294002（两种磷脂酰肌醇(PI)-3激酶的特异性抑制剂）抑制。此外，血小板衍生生长因子（PDGF）可以阻止表达野生型PDGF受体的PC-12细胞的凋亡，但不能阻止表达无法激活PI-3激酶的突变受体的细胞的凋亡。因此，细胞存活似乎是由不同于介导分化的PI-3激酶信号通路介导的。
Nerve growth factor (NGF) induces both differentiation and survival of neurons by binding to the Trk receptor protein tyrosine kinase. Although Pas is required for differentiation, it was not required for NGF-mediated survival of rat pheochromocytoma PC-12 cells in serum-free medium. However, the ability of NGF to prevent apoptosis (programmed cell death) was inhibited by wortmannin or LY294002, two specific inhibitors of phosphatidylinositol (PI)-3 kinase. Moreover, platelet-derived growth factor (PDGF) prevented apoptosis of PC-12 cells expressing the wild-type PDGF receptor, but not of cells expressing a mutant receptor that failed to activate PI-3 kinase. Cell survival thus appears to be mediated by a PI-3 kinase signaling pathway distinct from the pathway that mediates differentiation.