SIMILARITIES AND DIFFERENCES IN THE WAY NEUROTROPHINS INTERACT WITH THE TRK RECEPTORS IN NEURONAL AND NONNEURONAL CELLS
SIMILARITIES AND DIFFERENCES IN THE WAY NEUROTROPHINS INTERACT WITH THE TRK RECEPTORS IN NEURONAL AND NONNEURONAL CELLS
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DOI：
10.1016/0896-6273(93)90306-c
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发表时间：
1993-02-01
期刊：
影响因子：
16.2
通讯作者：
YANCOPOULOS, GD
中科院分区：
文献类型：
--
作者：
IP, NY;STITT, TN;YANCOPOULOS, GD
我们已经利用了一系列的方法来解决一些争议，伴随着神经生长因子（NGF）家族的神经营养因子的扩展和识别的Trk酪氨酸激酶作为这些因子的受体。例如，我们发现最近克隆的哺乳动物神经营养因子，称为神经营养因子-4或神经营养因子-5，并分配了广泛不同的受体特异性，代表了非洲爪蟾神经营养因子-4的功能对应物，并且是TrkB的“首选”配体。然而，它与TrkB的相互作用可以与脑源性神经营养因子（BDNF）与TrkB的相互作用区分开来。我们还发现，与非神经元细胞相比，所有Trk在神经元细胞中对其“优选"配体显示出相似的剂量反应（即，NGF用于TrkA，BDNF和NT-4/5用于TrkB，以及NT-3用于TrkC），提供了反对在神经元中表达的辅助分子在产生受体中的作用的证据，所述受体将允许对较低浓度的神经营养因子的响应。然而，我们发现神经元环境确实限制了Trks对它们的“非首选”神经营养因子配体的反应能力。
We have exploited a battery of approaches to address several controversies that have accompanied the expansion of the nerve growth factor (NGF) family of neurotrophic factors and the identification of the Trk tyrosine kinases as receptors for these factors. For example, we find that a recently cloned mammalian neurotrophin, known as either neurotrophin-4 or neurotrophin-5 and assigned widely differing receptor specificities, represents the functional counterpart of Xenopus neurotrophin-4 and is a ''preferred'' ligand for TrkB. However, its interactions with TrkB can be distinguished from those of brain-derived neurotrophic factor (BDNF) with TrkB. We also find that all of the Trks display similar dose responses to their ''preferred'' ligands in neuronal as compared with nonneuronal cells (i.e., NGF for TrkA, BDNF and NT-4/5 for TrkB, and NT-3 for TrkC), providing evidence against a role for accessory molecules expressed in neurons in generating receptors that would allow for responses to lower concentrations of the neurotrophins. However, we find that a neuronal environment does restrict the Trks in their ability to respond to their ''nonpreferred'' neurotrophin ligands.