AATYK: A novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells
AATYK: A novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells
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DOI：
10.1038/sj.onc.1201575
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发表时间：
1997-12-18
期刊：
影响因子：
8
通讯作者：
Reddy, EP
中科院分区：
文献类型：
--
作者：
Gaozza, E;Baker, SJ;Reddy, EP
细胞凋亡或程序性细胞死亡是一个过程，其中发育或环境刺激激活遗传程序以实施一系列最终导致细胞死亡的事件，以研究髓样前体细胞凋亡期间诱导的基因的性质。我们利用了32 Dc 13细胞系，其来源于正常小鼠骨髓，是非致瘤性的和二倍体的。这些细胞严格依赖于IL-3生长，并且当缺乏IL-3时依赖于IL-3。然而，当将这些细胞转移到含有G-CSF的培养基中时，细胞数量增加3-5倍，并且在12天后，整个群体分化成粒细胞，随后凋亡性死亡，在我们寻找32 Dc 13细胞凋亡和/或终末分化过程中诱导的基因时，我们鉴定了一种称为AATYK（凋亡相关酪氨酸激酶）的新基因，其表达在IL-3剥夺以及G-CSF诱导的终末分化过程中显著上调。在这份报告中，我们描述了cDNA克隆的序列，来自该基因的mRNA转录本，这些研究表明，该基因编码的蛋白质与酪氨酸激酶结构域的N-末端和脯氨酸丰富的结构域的C-末端，我们还报道了该基因的表达在v-abl或bcr-abl转化的髓样细胞，当在没有IL-3的情况下生长时，其不能转化。然而，当这些细胞在DMSO的存在下温育时，AATYK表达在由v-abl基因转化的32 D细胞中被诱导，另一方面，DMSO不能诱导由bcr-abl癌基因转化的32 D细胞中的凋亡或AATYK表达，这表明AATYK表达可能是诱导骨髓前体细胞的生长停滞和/或凋亡的必要先决条件。
Apoptosis, or programmed cell death, is a process where developmental or environmental stimuli activate a genetic program to implement a series of events that culminate in cell death, To study the nature of genes that are induced during the apoptotic death of myeloid precursor cells. we utilized the 32Dc13 cell line, which is derived from normal mouse bone marrow, is non-tumorigenic and diploid, These cells are strictly dependent on IL-3 for growth and apoptose when deprived of IL-3, However, when these cells are transferred to medium containing G-CSF, the cell number increases 3-5-fold and after 12 days the entire population is differentiated into granulocytes followed by apoptotic death, In our search for genes that are induced during apoptosis and/or terminal differentiation of 32Dc13 cells, we identified a novel gene termed AATYK (Apoptosis Associated Tyrosine Kinase), whose expression is dramatically upregulated during IL-3 deprivation as well as G-CSF-induced terminal differentiation. In this report, we describe the sequence of the cDNA clone, derived from the mRNA transcript of this gene, These studies show that this gene encodes a protein with a tyrosine kinase domain at the N-terminal end and a proline-rich domain at the C-terminal end, We also report that the expression of this gene is blocked in v-abl or bcr-abl transformed myeloid cells which are unable to apoptose when grown in the absence of IL-3, However, AATYK expression is induced in 32D cells transformed by the v-abl gene when these cells are incubated in the presence of DMSO, which induces growth arrest and apoptotic death of the cells, On the other hand, DMSO fails to induce apoptosis or AATYK expression in 32D cells transformed by the bcr-abl oncogene, suggesting that AATYK expression may be a necessary pre-requisite for the induction of growth arrest and/or apoptosis of myeloid precursor cells.