Snijders A J, Haase V H, Bernards A
Molecular Genetics Laboratory, Massachusetts General Hospital Cancer Center, Boston 02129.
Oncogene. 1993 Jan;8(1):27-35.
Two alternatively spliced mouse lymphocyte and brain ltk cDNAs predict small transmembrane tyrosine kinases that use CUG translational start codons and that differ upstream of their transmembrane segment. A recently isolated human neuroblastoma ltk cDNA, in contrast, includes a regular AUG start codon and predicts a more conventional receptor kinase with a larger N-terminal segment. This raised the suggestion that previous mouse cDNAs may have been aberrantly spliced or incomplete and questioned the significance of a recent study that localized the lymphoid ltk protein to the endoplasmic reticulum. Here we show that mice tissue-specifically express four ltk mRNAs. In addition to the two previously described lymphoid and brain mRNAs, we now describe two mRNAs from C1300 neuroblastoma cells that start with five exons which are absent from lymphoid or brain transcripts. The pair of C1300 mRNAs differ by the same alternatively spliced exon that distinguishes brain from lymphoid mRNAs and predict much larger receptor-type kinases that use regular AUG start codons. Our results also show that at least one of the larger, more conventional C1300 ltk receptors shares the endoplasmic reticulum localization of the shorter lymphoid protein.
两种选择性剪接的小鼠淋巴细胞和脑ltk cDNA预测出使用CUG翻译起始密码子的小跨膜酪氨酸激酶,且在其跨膜区段上游存在差异。相比之下,最近分离出的人类神经母细胞瘤ltk cDNA包含常规的AUG起始密码子,并预测出一种具有更大N端区段的更传统的受体激酶。这引发了一种观点,即之前的小鼠cDNA可能存在异常剪接或不完整的情况,并对最近一项将淋巴样ltk蛋白定位到内质网的研究的意义提出了质疑。在这里,我们表明小鼠组织特异性地表达四种ltk mRNA。除了之前描述的两种淋巴样和脑mRNA外,我们现在描述了来自C1300神经母细胞瘤细胞的两种mRNA,它们起始于五个外显子,而淋巴样或脑转录本中没有这些外显子。这对C1300 mRNA因相同的选择性剪接外显子而有所不同,该外显子区分了脑mRNA和淋巴样mRNA,并预测出使用常规AUG起始密码子的大得多的受体型激酶。我们的结果还表明,至少一种更大、更传统的C1300 ltk受体与较短的淋巴样蛋白共享内质网定位。