Human protein-tyrosine kinase gene HCK: expression and structural analysis of the promoter region.
Human protein-tyrosine kinase gene HCK: expression and structural analysis of the promoter region.
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发表时间：
1992-05
期刊：
影响因子：
8
通讯作者：
U. Lichtenberg;N. Quintrell;J. Bishop
中科院分区：
文献类型：
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作者：
U. Lichtenberg;N. Quintrell;J. Bishop
脊椎动物基因HCK编码与原癌基因SRC的产物密切相关的蛋白酪氨酸激酶。 HCK 主要在单核细胞和粒细胞造血细胞中表达，与这些细胞的分化相协调。在这里，我们报告了人类 HCK 表达控制机制的初步描述。分化过程中基因的诱导表现为 HCK RNA 和蛋白质产物稳态水平的增加。 RNA的积累显然是转录本身调节的结果，因为转录本的稳定性没有发生变化。转录在多个位点开始，呈簇状 c． HCK第一个内含子上游145个核苷酸。确定了主要起始位点上游 660 bp 的序列，揭示了 Sp1 和 AP-2 转录因子的候选结合位点，但 TATA 和 CAAT 元件都没有。与小鼠 hck 基因座的相同区域的比较显示出五个相似的小区域，其中只有两个区域在两个序列之间在拓扑上相似。 HCK 的表达似乎主要是通过控制转录来调节的，但在分化过程中实现组织特异性表达和转录增加的机制仍有待探索。
The vertebrate gene HCK encodes a protein-tyrosine kinase that is closely related to the product of the proto-oncogene SRC. HCK is expressed principally in monocytic and granulocytic hematopoietic cells, in coordination with differentiation of these cells. Here we report an initial description of the mechanisms by which expression of human HCK is controlled. Induction of the gene during differentiation was manifested by an increase in the steady-state levels of HCK RNA and protein product. The accumulation of RNA apparently resulted from modulation of transcription itself, since no change occurred in the stability of the transcripts. Transcription initiated at multiple sites, clustered c. 145 nucleotides upstream of the first intron of HCK. The sequence of 660 bp upstream of the major initiation site was determined, revealing candidate binding sites for Sp1 and AP-2 transcription factors, but neither TATA nor CAAT elements. Comparison to the same region of the mouse hck locus showed five small regions of similarity, only two of which were topographically analogous between the two sequences. It appears that expression of HCK is regulated primarily through control of transcription, but the mechanisms by which tissue-specific expression and increase of transcription during differentiation are achieved remain to be explored.