Ichaso N, Rodriguez R E, Martin-Zanca D, Gonzalez-Sarmiento R
Unidad de Medicina Molecular-Departamento de Medicina, Universidad de Salamanca, Spain.
Oncogene. 1998 Oct 8;17(14):1871-5. doi: 10.1038/sj.onc.1202100.
The trkC gene encodes the high-affinity receptor for neurotrophin 3 and plays an important role in the regulation of the survival and differentiation of the mammalian nervous system and in heart development. Chromosomal rearrangements of trkC have been recently reported in congenital fibrosarcoma and it has been proposed that abnormal activation of this gene might be involved in tumor development. To facilitate the search for new mutations and rearrangements in the human trkC locus we have partially characterized its genomic organization by restriction mapping and have obtained the complete intron-exon structure. Our results show that human trkC consists of 20 exons, including two that encode the inserts present in the extracellular and tyrosine kinase domains, and another two that encode the carboxyl-terminal tail of the truncated TRKC isoform. Analysis of the 5' flanking region revealed the absence of TATA box, a very high content in C/G compatible with a CpG island and the presence of putative binding sites for the AP1, AP2, GC, ATF, BRN2, AML1 and Nkx2.5 transcription factors.
trkC基因编码神经营养因子3的高亲和力受体，在调节哺乳动物神经系统的存活和分化以及心脏发育中发挥重要作用。最近有报道称先天性纤维肉瘤中存在trkC的染色体重排，有人提出该基因的异常激活可能与肿瘤发展有关。为便于在人类trkC基因座中寻找新的突变和重排，我们通过限制性图谱分析对其基因组结构进行了部分表征，并获得了完整的内含子-外显子结构。我们的结果表明，人类trkC由20个外显子组成，其中包括两个编码存在于细胞外和酪氨酸激酶结构域中的插入片段的外显子，以及另外两个编码截短的TRKC异构体羧基末端尾巴的外显子。对5'侧翼区域的分析显示，不存在TATA盒，C/G含量非常高，与一个CpG岛相符，并且存在AP1、AP2、GC、ATF、BRN2、AML1和Nkx2.5转录因子的假定结合位点。
