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Journal of Lipid Research, Vol. 47, 1940-1949, September 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology
Characterization of the human patatin-like phospholipase family
* Bioinformatics Discovery and Analysis, GlaxoSmithKline Research and Development, Stevenage, England SG1 2NY
Disease and Biomarker Transcriptomics, GlaxoSmithKline Research and Development, Stevenage, England SG1 2NY
Quantitative Expression, GlaxoSmithKline Research and Development, Upper Providence, Collegeville, PA 19426
** Laboratoires GlaxoSmithKline, Centre de Recherches, 91951 Les Ulis, France
The online version of this article (available at http://www.jlr.org) contains supplemental data.
Published, JLR Papers in Press, June 25, 2006.
1 To whom correspondence should be addressed. e-mail: paw84313{at}gsk.com
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.
Supplementary key words patatin-like phospholipase • adiponutrin • desnutrin • neuropathy target esterase • phospholipase A2, group VI • Intracellular membrane-associated calcium-independent phospholipase A2
• adipocyte • TaqMan • Affymetrix
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