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通过Trks和p75的神经营养因子信号传导

Neurotrophin signaling via Trks and p75.

作者信息

Friedman W J, Greene L A

机构信息

Department of Pathology, Center for Neurobiology and Behavior and Taub Center for Alzheimer's Disease Research, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, New York, 10032, USA.

出版信息

Exp Cell Res. 1999 Nov 25;253(1):131-42. doi: 10.1006/excr.1999.4705.

Abstract

This review focuses on recent advances in our understanding of receptor-mediated signaling by the neurotrophins NGF, BDNF, NT3, and NT4/5. Two distinct receptor types have been distinguished, Trks and p75. The Trks are receptor tyrosine kinases that utilize a complex set of substrates and adapter proteins to activate defined secondary signaling cascades required for neurotrophin-promoted neuronal differentiation, plasticity, and survival. A specialized aspect of Trk/neurotrophin action in neurons is the requirement for retrograde signaling from the distal periphery to the cell body. p75 is a universal receptor for neurotrophins that is a member of the TNF receptor/Fas/CD40 superfamily. p75 appears to modify Trk signaling when the two receptor types are coexpressed. When expressed in the absence of Trks, p75 mediates responses to neurotrophins including promotion of apoptotic death. The mechanisms of p75 receptor signaling remain to be fully understood.

摘要

本综述聚焦于我们对神经营养因子NGF、BDNF、NT3和NT4/5介导的受体信号传导的最新认识进展。已区分出两种不同的受体类型,即Trks和p75。Trks是受体酪氨酸激酶,它们利用一组复杂的底物和衔接蛋白来激活神经营养因子促进神经元分化、可塑性和存活所需的特定二级信号级联反应。Trk/神经营养因子在神经元中的作用的一个特殊方面是需要从远端外周向细胞体进行逆向信号传导。p75是神经营养因子的通用受体,是TNF受体/Fas/CD40超家族的成员。当两种受体类型共表达时,p75似乎会修饰Trk信号传导。当在没有Trks的情况下表达时,p75介导对神经营养因子的反应,包括促进凋亡性死亡。p75受体信号传导的机制仍有待充分了解。

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