Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system
Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system
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DOI：
10.1038/sj.onc.1200849
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发表时间：
1997-01-30
期刊：
影响因子：
8
通讯作者：
Yamamoto, T
中科院分区：
文献类型：
--
作者：
Iwahara, T;Fujimoto, J;Yamamoto, T
2; 5染色体易位经常与对变性大细胞淋巴瘤（ALCL）相关。易位创建了一个融合基因，该基因由ALK（变性淋巴瘤激酶）基因和核酚蛋白（NPM）基因组成：源自染色体2的ALK的3'一半被融合到NPM 5'的NPM 5'部分，该研究是5'YSTOMOMOSOMES研究。表明NPM-Alk融合基因的乘积是致癌的。为了帮助了解NPM-Alk癌基因如何转化细胞，重要的是要研究Alk基因产物的正常生物学功能Alk。在这里，我们显示了针对人和小鼠ALK蛋白的CDNA的分子克隆。推导的氨基酸序列表明，ALE是一种具有推定的跨膜结构域和细胞外域的新型受体蛋白酪氨酸激酶。这些序列在转化的NPM-Alk基因的乘积中不存在，ALK显示出与LTK（白细胞酪氨酸激酶）的最大序列相似性，其生物学功能目前尚不清楚。各种组织的RNA印迹杂交分析表明，在大脑和脊髓中主要检测到ALK mRNA。 ALK在新生儿大脑中高表达的抗血管抗体鞋的免疫印迹。此外，RNA原位杂交分析表明，在神经系统的特定区域中，ALK mRNA主要表达在神经元中，例如丘脑，中脑，中脑，嗅球和胚胎和新生小鼠的神经节，这些数据表明ALE Plays AL在大脑发展中的重要作用，并在神经系统中对特定神经元发挥作用。
The 2;5 chromosomal translocation is frequently associated with anaplastic large cell lymphomas (ALCLs). The translocation creates a fusion gene consisting of the alk (anaplastic lymphoma kinase) gene and the nucelophosmin (npm) gene: the 3' half of alk derived from chromosome 2 is fused to the 5' portion of npm from chromosome 5, A recent study shows that the product of the npm-alk fusion gene is oncogenic. To help understand how the npm-alk oncogene transform cells, it is important to investigate the normal biological function of the alk gene product, ALK. Here, we show molecular cloning of cDNAs for both the human and mouse ALK proteins. The deduced amino acid sequences reveal that ALE is a novel receptor protein-tyrosine kinase having a putative transmembrane domain and an extracellular domain. These sequences are absent in the product of the transforming npm-alk gene, ALK shows the greatest sequence similarity to LTK (leukocyte tyrosine kinase) whose biological function is presently unknown. RNA blot hybridization analysis of various tissues reveals that the alk mRNA is dominantly detected in the brain and spinal cord. Immunoblotting with anti-ALK antibody shoes that ALK is highly expressed in the neonatal brain. Furthermore, RNA in situ hybridization analysis shows that the alk mRNA is dominantly expressed in neurons in specific regions of the nervous system such as the thalamus, mid-brain, olfactory bulb, and ganglia of embryonic and neonatal mice, These data suggest that ALE plays an important role(s) in the development of the brain and exerts its effects on specific neurons in the nervous system.