JNK inhibitory kinase is up‐regulated in retinal ganglion cells after axotomy and enhances BimEL expression level in neuronal cells

JNK inhibitory kinase is up‐regulated in retinal ganglion cells after axotomy and enhances BimEL expression level in neuronal cells
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轴索切除后视网膜神经节细胞中 JNK 抑制激酶上调,并增强神经元细胞中 BimEL 表达水平

DOI:
10.1111/j.1471-4159.2005.03389.x
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发表时间:
2005
影响因子:
4.7
通讯作者:
T. Oshika
T. Oshika
中科院分区:
医学2区
文献类型:
--
作者:
T. Wakabayashi;J. Kosaka;T. Oshika

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视神经切断导致成年哺乳动物视网膜神经节细胞(RGC)的基因表达改变后死亡。为了阐明轴突切断诱导RGC死亡的分子机制,我们分离了视神经切断后上调的分子。其中之一,轴突切断相关基因(ARG)357,一个895个氨基酸的蛋白质,含有完整的丝氨酸-苏氨酸激酶结构域,是从大鼠视网膜的消减文库中分离出来的。序列显示,该基因是人类c-Jun N-末端激酶(JNK)抑制激酶的大鼠同源物,因此属于Sterile 20 s蛋白激酶的生发中心激酶-VIII亚家族。我们将ARG 357命名为大鼠JNK抑制激酶(JIK)。大鼠JIK在多种组织中广泛表达,在视网膜中高度表达,并在RGCs中选择性表达。轴突切断后,BimEL和Hrk(仅BH 3蛋白)和大鼠JIK在RGC中上调。在神经元细胞中过表达大鼠JIK上调BimEL的表达,但不上调Hrk的表达。这些结果表明,JIK可能通过上调BH 3-only蛋白的表达而导致轴突切断诱导的RGC死亡。
Optic nerve transection results in retinal ganglion cell (RGC) death in adult mammals, after the alteration of gene expression of RGCs. To elucidate the molecular mechanism by which axotomy induces RGC death, we isolated the molecules up‐regulated after optic nerve transection. One of these, axomtomy‐related gene (ARG)357, an 895‐amino‐acid protein containing a complete serine–threonine kinase domain, was isolated from a subtraction library of the rat retina. The sequence showed that this gene was a rat homolog of human c‐Jun N‐terminal kinase (JNK) inhibitory kinase and so belonged to the germinal center kinase‐VIII subfamily of Sterile20s protein kinase. We designated ARG357 as rat JNK inhibitory kinase (JIK). Rat JIK was expressed ubiquitously in various tissues and was highly expressed in the retina, with selective expression in RGCs. After axotomy, BimEL and Hrk, which are BH3‐only proteins, and rat JIK were up‐regulated in RGCs. Overexpression of rat JIK in neuronal cells up‐regulated the expression of BimEL, but not that of Hrk. These results indicate that JIK may contribute to axotomy‐induced RGC death by up‐regulating the expression of BH3‐only protein.
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