[Cloning and characterization of a novel cardiac-specific kinase gene p93 related to sarcomere].

Xian-Min Meng, Yong Zhao, Ying-Jie Wei, Hui-Qing Cao, Xiu-Wen Zhao, Dong-Qing Liu, Na Shi, Jin-Feng Ding
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Abstract

Myocyte's contraction is regulated by signal transduction pathway composed with many protein factors, but the definite mechanism is still uncertain. A novel cardiac-specific kinase gene which participates in regulation of signal transduction, p93 named, was cloned from adult heart cDNA library. p93, coding a family member of MAPKKK, localized on 1p31.1 based on bioinformatics analyses. Northern blot and 76-tissue array analyses determined that p93 was merely expressed in heart, but was undetectable in other tissues. Immunohistochemical study showed that p93 predominantly localized in the nucleus of cardiac myocytes. In vitro kinase assay indicated that p93 was a functional kinase capable of autophosphorylation. p93 could directly interact with cardiac troponin I by yeast two-hybrid system assessed utilizing bait plasmid containing p93 C-terminus (733 835 aa) and results were further confirmed by co-immunoprecipitation in vivo. Our data suggest that p93 is a cardiac-specific kinase and may play important role in regulation of sarcomeric contraction protein with signal transduction pathway similar ILK.

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[一种与肌瘤相关的心脏特异性激酶基因p93的克隆和表征]。
肌细胞的收缩受多种蛋白因子组成的信号转导通路调控,但其具体机制尚不明确。从成人心脏cDNA文库中克隆了一个参与信号转导调控的心脏特异性激酶基因p93。p93编码了MAPKKK家族成员,通过生物信息学分析定位在1p31.1上。Northern blot和76-组织阵列分析确定p93仅在心脏中表达,但在其他组织中未检测到。免疫组化研究显示p93主要定位于心肌细胞核。体外激酶实验表明p93是一个具有自磷酸化功能的激酶。利用含有p93 c端(733 835 aa)的诱饵质粒,通过酵母双杂交系统对p93与心肌肌钙蛋白I直接相互作用进行了评价,并通过体内共免疫沉淀进一步证实了这一结果。我们的数据表明p93是一种心脏特异性激酶,可能在与ILK类似的信号转导途径中调控肌肉收缩蛋白发挥重要作用。
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