A human homolog of mouse Lbh gene, hLBH, expresses in heart and activates SRE and AP-1 mediated MAPK signaling pathway
A human homolog of mouse Lbh gene, hLBH, expresses in heart and activates SRE and AP-1 mediated MAPK signaling pathway
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DOI：
10.1007/s11033-007-9068-4
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发表时间：
2008-06-01
影响因子：
2.8
通讯作者：
Wu, Xiushan
中科院分区：
文献类型：
--
作者：
Ai, Jianping;Wang, Yuequn;Wu, Xiushan
据报道，小鼠Lbh（肢体芽和心脏）可以通过调节心脏关键转录因子的组合活性以及它们在心脏发生中的个体功能来调节心脏基因的表达。在这里，我们报道了从人类胚胎心脏cDNA文库中克隆和鉴定小鼠Lbh基因的人类同源物，hLBH。hLBH的cDNA全长2927bp，编码一个含有105个氨基酸的蛋白产物。从斑马鱼到老鼠，再到人类，这种蛋白质在不同物种的进化中都是高度保守的。Northern blot分析表明，一个2.9 kb的hLBH特异性转录本在胚胎和成人心脏组织中都是最丰富表达的。在COS-7细胞中，hLBH蛋白定位于细胞核和细胞质。当融合到Gal-4 dna结合域时，hLBH是一个转录激活子。缺失分析表明，含有脯氨酸依赖的丝氨酸/苏氨酸激酶基团的n端和含有ERK d结构域基序的c端都是转录激活所必需的。在COS-7细胞中，hLBH的过表达激活了激活蛋白-1 （AP-1）和血清反应元件（SRE）的转录活性。这些结果表明，hLBH蛋白可能在丝裂原激活的蛋白激酶信号通路中作为转录激活因子介导细胞功能。
It has been reported that mouse Lbh (limb-bud and heart) can regulate cardiac gene expression by modulating the combinatorial activities of key cardiac transcription factors, as well as their individual functions in cardiogenesis. Here we report the cloning and characterization of the human homolog of mouse Lbh gene, hLBH, from a human embryonic heart cDNA library. The cDNA of hLBH is 2927 bp long, encoding a protein product of 105 amino acids. The protein is highly conserved in evolution across different species from zebra fish, to mouse, to human. Northern blot analysis indicates that a 2.9 kb transcript specific for hLBH is most abundantly expressed in both embryonic and adult heart tissue. In COS-7 cells, hLBH proteins are localized to both the nucleus and the cytoplasm. hLBH is a transcription activator when fused to Gal-4 DNA-binding domain. Deletion analysis indicates that both the N-terminal containing proline-dependent serine/threonine kinase group and the C-terminal containing ERK D-domain motif are required for transcriptional activation. Overexpression of hLBH in COS-7 cells activates the transcriptional activities of activator protein-1 (AP-1) and serum response element (SRE). These results suggest that hLBH proteins may act as a transcriptional activator in mitogen-activated protein kinase signaling pathway to mediate cellular functions.