The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance

被引:731
作者
Robson S.C. [1 ]
Sévigny J. [2 ]
Zimmermann H. [3 ]
机构
[1] Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
[2] Centre de Recherche en Rhumatologie et Immunologie, Université Laval, Québec, QC
[3] Institut fuer Zellbiologie und Neurowissenschaft, Biozentrum der J.W. Goethe-Universitaet, Frankfurt am Main D-60439
基金
美国国家卫生研究院; 加拿大健康研究院;
关键词
Apyrase; Brain; CD39; Ecto-ATPase; Immunology; Ischemia; Kidney; Liver; Nervous tissue; NTPDase; Platelet; Vasculature;
D O I
10.1007/s11302-006-9003-5
中图分类号
学科分类号
摘要
Ectonucleotidases are ectoenzymes that hydrolyze extracellular nucleotides to the respective nucleosides. Within the past decade, ectonucleotidases belonging to several enzyme families have been discovered, cloned and characterized. In this article, we specifically address the cell surface-located members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) family (NTPDase1,2,3, and 8). The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtype-specific antibodies have resulted in considerable insights into enzyme structure and function. These advances also allow definition of physiological and patho-physiological implications of NTPDases in a considerable variety of tissues. Biological actions of NTPDases are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides and consequent effects on P2-receptor signaling. It further appears that the spatial and temporal expression of NTPDases by various cell types within the vasculature, the nervous tissues and other tissues impacts on several patho-physiological processes. Examples include acute effects on cellular metabolism, adhesion, activation and migration with other protracted impacts upon developmental responses, inclusive of cellular proliferation, differentiation and apoptosis, as seen with atherosclerosis, degenerative neurological diseases and immune rejection of transplanted organs and cells. Future clinical applications are expected to involve the development of new therapeutic strategies for transplantation and various inflammatory cardiovascular, gastrointestinal and neurological diseases. © Springer Science + Business Media B.V. 2006.
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页码:409 / 430
页数:21
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