Borasio G D, John J, Wittinghofer A, Barde Y A, Sendtner M, Heumann R
Max-Planck-Institut für Psychiatrie, Abteilung Neurochemie, Martinsried, Federal Republic of Germany.
Neuron. 1989 Jan;2(1):1087-96. doi: 10.1016/0896-6273(89)90233-x.
Although evidence obtained with the PC12 cell line has suggested a role for the ras oncogene proteins in the signal transduction of nerve growth factor-mediated fiber outgrowth, little is known about the signal transduction mechanisms involved in the neuronal response to neurotrophic factors in nontransformed cells. We report here that the oncogene protein T24-ras, when introduced into the cytoplasm of freshly dissociated chick embryonic neurons, promotes the in vitro survival and neurite outgrowth of nerve growth factor-responsive dorsal root ganglion neurons, brain-derived neurotrophic factor-responsive nodose ganglion neurons, and ciliary neuronotrophic factor-responsive ciliary ganglion neurons. The proto-oncogene product c-Ha-ras also promotes neuronal survival, albeit less strongly. No effect could be observed with truncated counterparts of T24-ras and c-Ha-ras lacking the 23 C-terminal amino acids including the membrane-anchoring, palmityl-accepting cysteine. These results suggest a generalized involvement of ras or ras-like proteins in the intracellular signal transduction pathway for neurotrophic factors.
尽管利用PC12细胞系获得的证据表明，ras癌基因蛋白在神经生长因子介导的纤维生长的信号转导中发挥作用，但对于未转化细胞中神经元对神经营养因子的反应所涉及的信号转导机制，人们了解甚少。我们在此报告，癌基因蛋白T24-ras被导入刚解离的鸡胚神经元的细胞质中时，可促进对神经生长因子有反应的背根神经节神经元、对脑源性神经营养因子有反应的结状神经节神经元以及对睫状神经营养因子有反应的睫状神经节神经元的体外存活和神经突生长。原癌基因产物c-Ha-ras也能促进神经元存活，尽管作用较弱。缺少包括膜锚定、棕榈酰化接受半胱氨酸在内的23个C末端氨基酸的T24-ras和c-Ha-ras的截短对应物未观察到任何作用。这些结果表明，ras或类ras蛋白普遍参与神经营养因子的细胞内信号转导途径。
