DIFFERENTIAL EXPRESSION OF NERVE GROWTH-FACTOR RECEPTORS LEADS TO ALTERED BINDING-AFFINITY AND NEUROTROPHIN RESPONSIVENESS
DIFFERENTIAL EXPRESSION OF NERVE GROWTH-FACTOR RECEPTORS LEADS TO ALTERED BINDING-AFFINITY AND NEUROTROPHIN RESPONSIVENESS
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DOI：
10.1073/pnas.90.16.7859
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发表时间：
1993-08-15
影响因子：
11.1
通讯作者：
CHAO, MV
中科院分区：
文献类型：
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作者：
BENEDETTI, M;LEVI, A;CHAO, MV
低亲和力p75神经营养因子受体被认为与Trk受体酪氨酸激酶一起参与神经生长因子（NGF）的高亲和力结合位点的形成。为了研究两种NGF受体的功能意义，在PC12大鼠嗜铬细胞瘤细胞中稳定表达截短的p75受体，产生具有大大降低的野生型p75水平和正常Trk水平的细胞。虽然这些细胞能够正常分化的神经生长因子，非常少的高亲和力的神经生长因子结合位点被检测到。这些发现表明，高亲和力结合可能在功能上与生物反应分离。此外，观察到对神经营养因子3的反应性增加，表现为神经突生长增加。这些结果表明，正确的比例p75和p140trk是需要创建高亲和力的网站和p75的表达可能有助于相关的，但不同的神经营养因子之间的歧视。
The low-affinity p75 neurotrophin receptor is believed to participate with the Trk receptor tyrosine kinase in the formation of high-affinity binding sites for nerve growth factor (NGF). To investigate the functional significance of the two NGF receptors, a truncated p75 receptor was stably expressed in PC12 rat pheochromocytoma cells, yielding cells with greatly reduced levels of wild-type p75 and normal Trk levels. Although these cells were capable of normal differentiation by NGF, very few high-affinity NGF binding sites were detected. These findings indicate that high-affinity binding may be functionally dissociated from biological responses. Furthermore, an increased responsiveness to neurotrophin 3 was observed, as manifested by increased neurite outgrowth. These results suggest that a correct ratio of p75 and p140trk is required to create high-affinity sites and that p75 expression may assist in the discrimination between related but different neurotrophin factors.