Yao R, Cooper G M
Division of Molecular Genetics, Dana-Farber Cancer Institute, Boston, MA, USA.
Science. 1995 Mar 31;267(5206):2003-6. doi: 10.1126/science.7701324.
Nerve growth factor (NGF) induces both differentiation and survival of neurons by binding to the Trk receptor protein tyrosine kinase. Although Ras 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 (Pl)-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 Pl-3 kinase. Cell survival thus appears to be mediated by a Pl-3 kinase signaling pathway distinct from the pathway that mediates differentiation.
神经生长因子（NGF）通过与Trk受体蛋白酪氨酸激酶结合，诱导神经元的分化和存活。虽然Ras是分化所必需的，但在无血清培养基中，它并非NGF介导的大鼠嗜铬细胞瘤PC - 12细胞存活所必需。然而，渥曼青霉素或LY294002（磷脂酰肌醇（Pl）-3激酶的两种特异性抑制剂）抑制了NGF预防细胞凋亡（程序性细胞死亡）的能力。此外，血小板衍生生长因子（PDGF）可预防表达野生型PDGF受体的PC - 12细胞凋亡，但不能预防表达无法激活Pl - 3激酶的突变受体的细胞凋亡。因此，细胞存活似乎是由一条不同于介导分化的途径的Pl - 3激酶信号通路介导的。
