Reinach F C, MacLeod A R
Nature. 1986;322(6080):648-50. doi: 10.1038/322648a0.
The trk oncogene is a human transforming gene generated by the fusion of tropomyosin gene sequence to a truncated tyrosine kinase receptor gene. We have now characterized the normal tropomyosin gene from which the trk oncogene is derived. At least two different transcripts are expressed by this gene using a tissue-specific alternative messenger RNA splicing mechanism: a 2.5-kilobase (kb) mRNA encoding a 248-amino-acid tropomyosin in human fibroblasts and a 1.3-kb mRNA encoding a 285-amino-acid tropomyosin in human skeletal muscle. The rearrangement which generates the trk oncogene preserves most of the tropomyosin-coding sequences of the normal gene, including exons alternatively spliced in muscle and non-muscle tissue. We therefore expect the trk oncogene to show a tissue-specific pattern of transforming activity. Correct expression of the trk oncogene can occur only in non-muscle tissues. In muscle tissue the oncogene would almost certainly be inactive, as splicing according to the alternative muscle pattern aborts synthesis of the tyrosine kinase domain.
trk癌基因是原肌球蛋白基因序列与截短的酪氨酸激酶受体基因融合产生的一种人类转化基因。我们现已鉴定出trk癌基因所源自的正常原肌球蛋白基因。该基因通过组织特异性可变信使核糖核酸剪接机制表达至少两种不同的转录本：一种2.5千碱基（kb）的信使核糖核酸，在人成纤维细胞中编码一种含248个氨基酸的原肌球蛋白；另一种1.3 kb的信使核糖核酸，在人骨骼肌中编码一种含285个氨基酸的原肌球蛋白。产生trk癌基因的重排保留了正常基因的大部分原肌球蛋白编码序列，包括在肌肉和非肌肉组织中可变剪接的外显子。因此，我们预计trk癌基因会表现出组织特异性的转化活性模式。trk癌基因的正确表达仅能在非肌肉组织中发生。在肌肉组织中，该癌基因几乎肯定是无活性的，因为按照可变肌肉模式进行的剪接会中止酪氨酸激酶结构域的合成。
