Verdi J M, Ip N, Yancopoulos G D, Anderson D J
Division of Biology, California Institute of Technology, Pasadena 91125.
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3949-53. doi: 10.1073/pnas.91.9.3949.
We have transfected MAH cells, an immortalized sympathoadrenal progenitor cell line, with a plasmid encoding the 140-kDa Trk protein, a nerve growth factor (NGF) receptor with protein-tyrosine kinase activity. NGF promotes neurite outgrowth and proliferation from such cells, indicating that Trk is sufficient to mediate such responses in the absence of significant levels of the endogenous 75-kDa low-affinity NGF receptor (p75). These initial NGF responses are indistinguishable from those evoked by basic fibroblast growth factor (bFGF). However, NGF is sufficient to promote terminal differentiation of a approximately 8% of trk-transfected MAH cells to postmitotic, NGF-dependent neurons, whereas all cells eventually die in medium with bFGF. Other environmental signals (such as depolarization or ciliary neurotrophic factor) can cooperate with NGF to enhance production of postmitotic NGF-dependent neurons in trk-transfected MAH cells. The terminal differentiation of sympathetic neurons thus involves sequential and cooperative actions of different growth and neurotrophic factors, as well as cell-intrinsic changes in the response to these factors.
我们用编码140-kDa Trk蛋白（一种具有蛋白酪氨酸激酶活性的神经生长因子（NGF）受体）的质粒转染了MAH细胞（一种永生化的交感肾上腺祖细胞系）。NGF可促进此类细胞的神经突生长和增殖，这表明在不存在显著水平的内源性75-kDa低亲和力NGF受体（p75）的情况下，Trk足以介导此类反应。这些最初的NGF反应与碱性成纤维细胞生长因子（bFGF）引发的反应无法区分。然而，NGF足以促进约8%的trk转染MAH细胞终末分化为有丝分裂后、依赖NGF的神经元，而所有细胞最终在含有bFGF的培养基中死亡。其他环境信号（如去极化或睫状神经营养因子）可与NGF协同作用，增强trk转染MAH细胞中有丝分裂后依赖NGF的神经元的产生。因此，交感神经元的终末分化涉及不同生长和神经营养因子的顺序和协同作用，以及细胞对这些因子反应的内在变化。
