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人类类马铃薯块茎蛋白磷脂酶家族的特征分析

Characterization of the human patatin-like phospholipase family.

作者信息

Wilson Paul A, Gardner Scott D, Lambie Natalie M, Commans Stephane A, Crowther Daniel J

机构信息

Bioinformatics Discovery and Analysis, GlaxoSmithKline Research and Development, Stevenage, England SG1 2NY, UK.

出版信息

J Lipid Res. 2006 Sep;47(9):1940-9. doi: 10.1194/jlr.M600185-JLR200. Epub 2006 Jun 25.

Abstract

Several publications have described biological roles for human patatin-like phospholipases (PNPLAs) in the regulation of adipocyte differentiation. Here, we report on the characterization and expression profiling of 10 human PNPLAs. A variety of bioinformatics approaches were used to identify and characterize all PNPLAs encoded by the human genome. The genes described represent a divergent family, most with a highly conserved ortholog in several mammalian species. In silico characterization predicts that two of the genes function as integral membrane proteins and are regulated by cAMP/cGMP. A structurally guided protein alignment of the patatin-like domain identifies a number of conserved residues in all family members. Quantitative PCR was used to determine the expression profile of each family member. Affymetrix-based profiling of a human preadipocyte cell line identified several members that are differentially regulated during cell differentiation. Cumulative data suggest that patatin-like genes normally expressed at very low levels are induced in response to environmental signals. Given the observed conservation of the patatin fold and lipase motif in all human PNPLAs, a single nomenclature to describe the PNPLA family is proposed.

摘要

已有多篇文献描述了人类帕他汀样磷脂酶(PNPLAs)在脂肪细胞分化调控中的生物学作用。在此,我们报告了10种人类PNPLAs的特性及表达谱分析。我们运用了多种生物信息学方法来鉴定和表征人类基因组编码的所有PNPLAs。所描述的基因代表了一个多样化的家族,其中大多数在几种哺乳动物物种中具有高度保守的直系同源基因。计算机模拟表征预测,其中两个基因作为整合膜蛋白发挥作用,并受cAMP/cGMP调控。对帕他汀样结构域进行基于结构的蛋白质比对,可识别出所有家族成员中的一些保守残基。我们使用定量PCR来确定每个家族成员的表达谱。基于Affymetrix技术对人前脂肪细胞系进行的分析表明,有几个成员在细胞分化过程中受到差异调控。累积数据表明,通常以极低水平表达的帕他汀样基因会因环境信号而被诱导表达。鉴于在所有人类PNPLAs中均观察到帕他汀折叠和脂肪酶基序的保守性,我们提出了一种描述PNPLA家族的单一命名法。

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