Carter M T, Yome J L, Marcil M N, Martin C A, Vanhorne J B, Mulligan L M
Department of Pathology, Queen's University, Kingston, ON, Canada.
Cytogenet Cell Genet. 2001;95(3-4):169-76. doi: 10.1159/000059341.
The RET proto-oncogene encodes a receptor tyrosine kinase required for development of the kidney and neural crest-derived cell types. Alternative splicing of the 3' exons of human RET results in three protein isoforms with distinct C-termini: RET9, RET51, and RET43. These RET isoforms show differential binding to downstream adapter molecules, suggesting they may have distinct signaling functions. We have characterized Ret 3' sequences in mouse and investigated alternative splicing of this region. We found that the organization of Ret 3' sequences is very similar to human RET. The mouse locus also has alternatively spliced C-terminal coding regions, and the sequences corresponding to RET9 and RET51 are highly conserved in both position and sequence with the human locus. Further, we compared the predicted C-terminal amino acids of RET9 and RET51 in seven vertebrate species, and found that they are well conserved. We have identified sequence encoding a putative ret43 isoform in mouse, however the predicted amino acid sequence showed low homology to human RET43. Our data suggest that RET isoforms are evolutionarily highly conserved over a broad range of species, which may indicate that each isoform has a distinct role in normal RET function.
RET原癌基因编码一种受体酪氨酸激酶，该激酶是肾脏和神经嵴衍生细胞类型发育所必需的。人类RET基因3'外显子的可变剪接产生了三种具有不同C末端的蛋白质异构体：RET9、RET51和RET43。这些RET异构体对下游衔接分子表现出不同的结合，表明它们可能具有不同的信号传导功能。我们已经对小鼠中的Ret 3'序列进行了表征，并研究了该区域的可变剪接。我们发现Ret 3'序列的组织与人RET非常相似。小鼠基因座也有可变剪接的C末端编码区域，并且与RET9和RET51相对应的序列在位置和序列上与人基因座高度保守。此外，我们比较了七个脊椎动物物种中RET9和RET51的预测C末端氨基酸，发现它们高度保守。我们在小鼠中鉴定出了编码假定的ret43异构体的序列，然而预测的氨基酸序列与人类RET43的同源性较低。我们的数据表明，RET异构体在广泛的物种中在进化上高度保守，这可能表明每种异构体在正常RET功能中具有独特的作用。
