Represa J, Avila M A, Miner C, Giraldez F, Romero G, Clemente R, Mato J M, Varela-Nieto I
Departamento Ciencias Morfológicas, Facultad de Medicina, Universidad de Valladolid, Spain.
Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8016-9. doi: 10.1073/pnas.88.18.8016.
Nerve growth factor (NGF) exerts a variety of actions during embryonic development. At the early stages of inner ear development, NGF stimulates cell proliferation, an effect mediated through low-affinity receptors. We have studied the possibility that the glycosyl-phosphatidylinositol/inositol phosphoglycan (glycosyl-PtdIns/IPG) system is involved in transmitting this NGF signal. Endogenous glycosyl-PtdIns was characterized in extracts of cochleovestibular ganglia (CVGs) that incorporated [3H]glucosamine, [3H]galactose, [3H]myristic acid, and [3H]palmitic acid. Incubation of CVG with NGF produced a rapid and transient hydrolysis of glycosyl-PtdIns. Hydrolysis was complete at 100 ng/ml, and the half-maximal effect occurred at 25 ng/ml, overlapping with the concentration dependence of the mitogenic effect of NGF. An IPG was isolated from embryonic extracts. It had biological effects similar to those reported for the insulin-induced IPG in other tissues. It exerted a powerful mitogenic effect on CVG, comparable to that of NGF. Both the IPG- and NGF-induced cell proliferation were blocked by anti-IPG antibodies that recognized the endogenous IPG on a silica plate immunoassay. These results show that CVG possesses a fully active glycosyl-PtdIns/IPG signal transduction system and that the proliferative effects associated with NGF binding to low-affinity receptors require IPG generation.
神经生长因子（NGF）在胚胎发育过程中发挥多种作用。在内耳发育的早期阶段，NGF刺激细胞增殖，这种作用是通过低亲和力受体介导的。我们研究了糖基磷脂酰肌醇/肌醇磷酸聚糖（糖基-PtdIns/IPG）系统参与传递这种NGF信号的可能性。通过掺入[3H]葡糖胺、[3H]半乳糖、[3H]肉豆蔻酸和[3H]棕榈酸，对内耳前庭神经节（CVG）提取物中的内源性糖基-PtdIns进行了表征。用NGF孵育CVG会导致糖基-PtdIns快速且短暂的水解。在100 ng/ml时水解完全，半数最大效应发生在25 ng/ml，这与NGF促有丝分裂作用的浓度依赖性重叠。从胚胎提取物中分离出一种IPG。它具有与其他组织中胰岛素诱导的IPG所报道的类似生物学效应。它对CVG具有强大的促有丝分裂作用，与NGF相当。在硅胶板免疫测定中，识别内源性IPG的抗IPG抗体可阻断IPG和NGF诱导的细胞增殖。这些结果表明，CVG拥有一个完全活跃的糖基-PtdIns/IPG信号转导系统，并且与NGF结合低亲和力受体相关的增殖效应需要IPG的产生。
