THE TRK FAMILY OF NEUROTROPHIN RECEPTORS
THE TRK FAMILY OF NEUROTROPHIN RECEPTORS
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DOI：
10.1002/neu.480251107
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发表时间：
1994-11-01
期刊：
影响因子：
--
通讯作者：
BARBACID, M
中科院分区：
文献类型：
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作者：
BARBACID, M
越来越多的证据表明，酪氨酸蛋白激酶受体 Trk 家族、Trk（也称为 TrkA）、TrkB 和 TrkC 负责介导神经营养素 NGF 家族的营养作用。神经生长因子 (NGF) 特异性识别 Trk，Trk 是在所有主要 NGF 靶标中识别的受体，包括交感神经节、三叉神经节和背根神经节以及基底前脑和纹状体的胆碱能神经元。脑源性神经营养因子 (BDNF) 和神经营养蛋白-4 (NT3) 特异性激活 TrkB 酪氨酸激酶受体。编码该受体的 trkB 转录物遍布中枢和周围神经系统的多个结构。 Neurotropin-3 (NT-3) 主要激活 TrkC 酪氨酸蛋白激酶，这是由 trkC 选择性剪接编码的四种相关亚型，trkC 是一种在整个哺乳动物神经系统中广泛表达的基因。与其他神经营养素不同，NT-3 似乎有些混杂，因为它可以激活 Trk 和 TrkB 激酶受体，至少在某些细胞系统中是这样。 trkB 和 trkC 基因还编码功能迄今未知的非催化神经营养蛋白受体亚型。最近，已经产生了缺乏这些酪氨酸激酶受体的小鼠品系。这些突变小鼠的初步表征提供了有关这些受体在哺乳动物神经系统个体发育中的作用的重要信息。例如，缺乏 Trk 受体的小鼠缺乏大多数交感神经元，并且不会表现出伤害性和温度感，这两种缺陷可能是由于其三叉神经节和背根神经节中严重的神经元细胞损失造成的。缺乏 TrkB 酪氨酸激酶受体的小鼠会因无法进食而在出生后死亡。三叉神经、结节和岩感觉神经节以及面部运动核中的神经元细胞损失可能导致这种表型。最后，TrkC 缺陷小鼠表现出与本体感觉丧失一致的惊人异常运动，这种缺陷可能是在这种突变小鼠中观察到的 Ia 肌肉传出完全丧失的结果。 (C) 1994 约翰威利父子公司
Accumulating evidence indicates that the Trk family of tyrosine protein kinase receptors, Trk (also known as TrkA), TrkB, and TrkC, are responsible for mediating the trophic effects of the NGF family of neurotrophins. Nerve growth factor (NGF) specifically recognizes Trk, a receptor identified in all major NGF targets, including sympathetic, trigeminal, and dorsal root ganglia as well as in cholinergic neurons of the basal forebrain and the striatum. Brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT3) specifically activate the TrkB tyrosine kinase receptor. trkB transcripts encoding this receptor are found throughout multiple structures of the central and peripheral nervous system. Neurotrophin-3 (NT-3) primarily activates the TrkC tyrosine protein kinases, four related isoforms encoded by alternative splicing of trkC, a gene also widely expressed throughout the mammalian nervous system. Unlike the other neurotrophins, NT-3 appears to be somewhat promiscuous since it can activate Trk and TrkB kinase receptors, at least in certain cell systems. The trkB and trkC genes also encode noncatalytic neurotrophin receptor isoforms of an as yet, unknown function. Recently, strains of mice lacking each of these tyrosine kinase receptors have been generated. Preliminary characterization of these mutant mice has provided significant information regarding the role of these receptors in the ontogeny of the mammalian nervous system. For instance, mice deficient for Trk receptors lack most sympathetic neurons and do not display nociceptive and temperature sensations, two defects likely to result from severe neuronal cell loss in their trigeminal and dorsal root ganglia. Mice lacking TrkB tyrosine kinase receptors die postnatally due to their inability to intake food. Neuron cell loss in their trigeminal, nodose and petrosal sensory ganglia as well as in the facial motor nucleus are likely to contribute to this phenotype. Finally, TrkC-deficient mice display strikingly abnormal movements consistent with loss of proprioception, a defect likely to be a consequence of the complete loss of Ia muscle efferents observed in this mutant mice. (C) 1994 John Wiley & Sons, Inc.