Expression of c-Fes protein isoforms correlates with differentiation in myeloid leukemias
Expression of c-Fes protein isoforms correlates with differentiation in myeloid leukemias
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DOI：
10.1089/dna.2005.24.311
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发表时间：
2005-05-01
影响因子：
3.1
通讯作者：
Yates, KE
中科院分区：
文献类型：
--
作者：
Carlson, A;Berkowitz, JM;Yates, KE
细胞fes基因编码一个93千道尔顿的蛋白酪氨酸激酶（p93），在正常和肿瘤性骨髓细胞中均有表达。增加的c-Fes表达与正常骨髓细胞和细胞系的分化相关。我们的假设是，原代白血病细胞在分化程度更高的细胞中表现出类似的表达增加模式。因此，我们比较了c-Fes在具有未分化的原始细胞表型（急性髓性白血病-AML）的细胞与具有分化的表型（慢性髓性白血病-CML）的细胞中的表达。而不是p93表达水平的差异，我们发现复杂的模式c-Fes免疫反应蛋白，对应于正常和白血病骨髓细胞的分化。“原始”模式由c-Fes免疫反应蛋白p93、p74和p70组成;“分化”模式显示另外两种c-Fes免疫反应蛋白p67和p62。使用来自小鼠和人细胞系的mRNA，我们发现c-fes mRNA中的一个或多个外显子缺失。这些缺失预测了参与蛋白质-蛋白质相互作用的保守结构域（CDC 15/FCH和SH 2）的截短。然而，在激酶结构域内没有发现缺失。我们推断，选择性剪接产生一个家庭的c-Fes蛋白。这可能是在骨髓细胞分化的特定阶段将c-Fes激酶结构域引导至不同亚细胞位置和/或底物的机制。
The cellular fes gene encodes a 93-kilodalton protein-tyrosine kinase (p93) that is expressed in both normal and neoplastic myeloid cells. Increased c-Fes expression is associated with differentiation in normal myeloid cells and cell lines. Our hypothesis was that primary leukemia cells would show a similar pattern of increased expression in more differentiated cells. Therefore, we compared c-Fes expression in cells with an undifferentiated, blast phenotype (acute myelogenous leukemia-AML) to cells with a differentiated phenotype (chronic myelogenous leukemia-CML). Instead of differences in p93 expression levels, we found complex patterns of c-Fes immunoreactive proteins that corresponded with differentiation in normal and leukemic myeloid cells. The "blast" pattern consisted of c-Fes immunoreactive proteins p93, p74, and p70; the "differentiated" pattern showed two additional c-Fes immunoreactive proteins, p67 and p62. Using mRNA from mouse and human cell lines, we found deletion of one or more exons in the c-fes mRNA. Those deletions predicted truncation of conserved domains (CDC15/FCH and SH2) involved in protein-protein interactions. No deletions were found, however, within the kinase domain. We infer that alternative splicing generates a family of c-Fes proteins. This may be a mechanism to direct the c-Fes kinase domain to different subcellular locations and/or substrates at specific stages of myeloid cell differentiation.