Takahashi M, Buma Y, Iwamoto T, Inaguma Y, Ikeda H, Hiai H
Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, Japan.
Oncogene. 1988 Nov;3(5):571-8.
The nucleotide sequence of the ret proto-oncogene has been determined from cDNA clones isolated from a cDNA library of a THP-1 human monocytic leukemia cell line. Analysis of this sequence indicates that it encodes a protein which is structurally related to transmembrane receptors with a cytoplasmic tyrosine kinase domain. Unlike most growth factor receptors, it contains two hydrophobic regions which are potential transmembrane domains. Comparison of the sequence of the ret proto-oncogene with that of the ret transforming gene revealed that, in addition to the amino-terminal truncation, the last 51 carboxy-terminal amino acids of the ret proto-oncogene were replaced with 9 unrelated amino acids of the ret transforming gene. The focus forming activity of the ret cDNA, containing both amino-terminal and caboxy-terminal truncations, was approximately 13-fold higher than that of cDNA containing only the amino-terminal truncation. This suggests a possible role for the carboxy-terminal sequence in activation of transforming potential of the ret proto-oncogene. When transcription of the ret proto-oncogene was examined in a variety of mouse tissues, we detected its transcription in normal mouse spinal cord and lymphadenopathy of C3H/HeJ-gld/gld and MRL/Mp-lpr/lpr mice.
已从人THP - 1单核细胞白血病细胞系的cDNA文库中分离出的cDNA克隆确定了原癌基因ret的核苷酸序列。对该序列的分析表明，它编码一种蛋白质，该蛋白质在结构上与具有细胞质酪氨酸激酶结构域的跨膜受体相关。与大多数生长因子受体不同，它包含两个疏水区域，这些区域是潜在的跨膜结构域。将原癌基因ret的序列与ret转化基因的序列进行比较发现，除了氨基末端截短外，原癌基因ret的最后51个羧基末端氨基酸被ret转化基因的9个不相关氨基酸所取代。包含氨基末端和羧基末端截短的ret cDNA的集落形成活性比仅包含氨基末端截短的cDNA高约13倍。这表明羧基末端序列在激活原癌基因ret的转化潜能中可能起作用。当在多种小鼠组织中检测原癌基因ret的转录时，我们在正常小鼠脊髓以及C3H/HeJ - gld/gld和MRL/Mp - lpr/lpr小鼠的淋巴结病中检测到了它的转录。
