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小鼠中蛋白磷酸酶2A的PR61/B'调节亚基的基因组组织、染色体定位、组织分布及发育调控

Genomic organisation, chromosomal localisation tissue distribution and developmental regulation of the PR61/B' regulatory subunits of protein phosphatase 2A in mice.

作者信息

Martens Ellen, Stevens Ilse, Janssens Veerle, Vermeesch Joris, Götz Jürgen, Goris Jozef, Van Hoof Christine

机构信息

Division of Biochemistry, Faculty of Medicine, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium.

出版信息

J Mol Biol. 2004 Feb 27;336(4):971-86. doi: 10.1016/j.jmb.2003.12.047.

DOI:10.1016/j.jmb.2003.12.047
PMID:15095873
Abstract

Protein phosphatase 2A (PP2A) is a major serine/threonine-specific phosphatase playing central roles in development, cell growth and transformation. Regulation is largely accomplished by the regulatory B subunits, which determine substrate specificity, subcellular localisation and catalytic activity. The B' family, also known as the PR61 family, is the most diverse, consisting of five genes (alpha,beta,gamma,delta and epsilon) that give rise to a number of splice variants. We deduced the sequences of the different PR61 proteins in mice and found evidence for the expression of PR61alpha, beta1, gamma1, gamma2, gamma3, delta1 and epsilon. We report the genomic organisation and localisation of the murine PR61 genes (Ppp2r5a-Ppp2r5e). This information will be useful for the future realisation of PR61 knockouts. Using Northern blotting, we examined the expression of the five PR61 isoforms in different tissues. A brain-specific function can be expected for the PR611beta protein based on the high expression levels observed in murine brain. In situ hybridisation analysis of the adult brain revealed a distinct and partially overlapping pattern of mRNA expression of the various PR61 isoforms. The PR61 mRNA expression during embryonic development was examined by Northern blotting. The PR61 transcripts were differentially expressed, suggesting a specific function for each of the PR61 proteins during embryonic development and/or adult life.

摘要

蛋白磷酸酶2A(PP2A)是一种主要的丝氨酸/苏氨酸特异性磷酸酶,在发育、细胞生长和转化过程中发挥核心作用。其调节主要由调节性B亚基完成,调节性B亚基决定底物特异性、亚细胞定位和催化活性。B'家族,也称为PR61家族,是最多样化的,由五个基因(α、β、γ、δ和ε)组成,这些基因产生许多剪接变体。我们推导了小鼠中不同PR61蛋白的序列,并发现了PR61α、β1、γ1、γ2、γ3、δ1和ε表达的证据。我们报告了小鼠PR61基因(Ppp2r5a - Ppp2r5e)的基因组组织和定位。这些信息将有助于未来实现PR61基因敲除。使用Northern印迹法,我们检测了五种PR61异构体在不同组织中的表达。基于在小鼠脑中观察到的高表达水平,可以预期PR61β蛋白具有脑特异性功能。对成年脑的原位杂交分析揭示了各种PR61异构体mRNA表达的独特且部分重叠的模式。通过Northern印迹法检测了胚胎发育过程中PR61 mRNA的表达。PR61转录本差异表达,表明每种PR61蛋白在胚胎发育和/或成年期具有特定功能。

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