Murine ecto-5'-nucleotidase (CD73): cDNA cloning and tissue distribution

Resta, Regina; Hooker, Scott W.; Hansen, Karl R.; Laurent, Aletha B.; Park, J. L.; Blackburn, Michael R.; Knudsen, Thomas B.; Thompson, Linda F.

doi:10.1016/0378-1119(93)90635-g

Cited by 76 publications

(50 citation statements)

References 26 publications

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“…During normal cell maturation, CD73 expression and its enzymatic activity increase (22,23). One of the known activators is the end product of the enzymatic activity of CD73 itself: adenosine increases CD73 expression and enzymatic activity in a paracrine fashion (24).…”

Section: Discussionmentioning

confidence: 99%

IFN-α Induced Adenosine Production on the Endothelium: A Mechanism Mediated by CD73 (Ecto-5′-Nucleotidase) Up-Regulation

Niemelä

Henttinen

Yegutkin

et al. 2004

The Journal of Immunology

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CD73 (ecto-5′-nucleotidase; EC 3.1.3.5) participates in lymphocyte binding to endothelial cells and converts extracellular AMP into a potent anti-inflammatory substance adenosine. However, the regulation of expression and function of CD73 has remained largely unknown. In this study, we show that IFN-α produces a time- and dose-dependent long-term up-regulation of CD73 on endothelial cells, but not on lymphocytes both at protein and RNA levels. Moreover, CD73-mediated production of adenosine is increased after IFN-α treatment on endothelial cells, resulting in a decrease in the permeability of these cells. Subsequent to induction with PMA, FMLP, dibutyryl cAMP, thrombin, histamine, IL-1β, TNF-α, and LPS, no marked changes in the level of CD73 expression on endothelial cells are observed. We also show that CD73 is up-regulated in vivo on the vasculature after intravesical treatment of urinary bladder cancers with IFN-α. In conclusion, distinct behavior of lymphocyte and endothelial CD73 subsequent to cytokine treatment further emphasizes the existence of cell type-specific mechanisms in the regulation of CD73 expression and function. Overall, these results suggest that IFN-α is a relevant in vivo regulator of CD73 in the endothelial-leukocyte microenvironment in infections/inflammations, and thus has a fundamental role in controlling the extent of inflammation via CD73-dependent adenosine production.

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Section: Discussionmentioning

confidence: 99%

IFN-α Induced Adenosine Production on the Endothelium: A Mechanism Mediated by CD73 (Ecto-5′-Nucleotidase) Up-Regulation

Niemelä

Henttinen

Yegutkin

et al. 2004

The Journal of Immunology

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“…The enzyme has a broad tissue distribution, and it is expressed by subpopulations of human T and B lymphocytes and also by a considerable variety of tumor cells [203]. Catalytic activity varies considerably between individual tissues [204]. The existence of both catalytically active and inactive forms of eN has been described which may result from differential posttranslational processing [205][206][207][208] or also from the interaction of the enzyme with extracellular matrix proteins (see below).…”

Section: Ecto-5′-nucleotidasementioning

confidence: 99%

“…The human cDNA encodes a precursor of 574 residues that is converted to the mature form of 523 residues after cleavage of the signal peptide and the hydrophobic domain at the C-terminus, which is replaced with the GPI anchor, similar to the enzymes cloned from rat [237] and mouse [204]. The nucleotide sequence of murine eN cDNA is 86 and 92 % identical to that of the human and rat cDNAs, respectively.…”

Section: Ecto-5′-nucleotidase Versus Soluble 5′-nucleotidasesmentioning

confidence: 99%

Cellular function and molecular structure of ecto-nucleotidases

Zimmermann

Zebisch

Sträter

2012

Purinergic Signalling

888

922

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Ecto-nucleotidases play a pivotal role in purinergic signal transmission. They hydrolyze extracellular nucleotides and thus can control their availability at purinergic P2 receptors. They generate extracellular nucleosides for cellular reuptake and salvage via nucleoside transporters of the plasma membrane. The extracellular adenosine formed acts as an agonist of purinergic P1 receptors. They also can produce and hydrolyze extracellular inorganic pyrophosphate that is of major relevance in the control of bone mineralization. This review discusses and compares four major groups of ectonucleotidases: the ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase, ecto-nucleotide pyrophosphatase/phosphodiesterases, and alkaline phosphatases. Only recently and based on crystal structures, detailed information regarding the spatial structures and catalytic mechanisms has become available for members of these four ecto-nucleotidase families. This permits detailed predictions of their catalytic mechanisms and a comparison between the individual enzyme groups. The review focuses on the principal biochemical, cell biological, catalytic, and structural properties of the enzymes and provides brief reference to tissue distribution, and physiological and pathophysiological functions.

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“…Other ecto-ATPases together with this enzyme form the cascade to finish the action of nucleotides such as ATP and extracellular signaling molecules acting on P2X and P2Y receptors. 5'-nucleotidase is present in basically all tissues and its primary structure has been determined in bovine and rat liver, electric ray brain, mouse kidney and human placenta, showing that the enzyme consists of 548 amino acids with a molecular mass varying between 62 and 74 kDa [90,105,128,135,144]. The protein occurs as a homodimer with interchain disulfide bridges and hydrolyzes a variety of nucleoside 5'-nucleoside monophosphates such as AMP, CMP, UMP, IMP and GMP.…”

Section: '-Nucleotidase: General Characteristicsmentioning

confidence: 99%

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

et al. 2007

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Abstract. Extracellular nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface-located group of enzymes called ectonucleotidases. There are four major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases and ecto-5'-nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and 5'-nucleotidase activities in disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes, hypertension, hypercholesterolemia and cancer, as well as in pathological conditions where platelets are less responsive, such as in chronic renal failure. In addition, immunomodulation and cell-cell interactions involving these enzymes are considered, as well as ATP and ADP hydrolysis under different clinical conditions related with alterations in the immune system, such as acute lymphoblastic leukemia (ALL), Bchronic lymphocytic leukemia (B-CLL) and infections associated with human immunodeficiency virus (HIV). Finally, changes in ATP, ADP and AMP hydrolysis induced by inborn errors of metabolism, seizures and epilepsy are discussed in order to highlight the importance of these enzymes in the control of neuronal activity in pathological conditions. Despite advances made toward understanding the molecular structure of ectonucleotidases, much more investigation will be necessary to entirely grasp their role in physiological and pathological conditions.

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Murine ecto-5'-nucleotidase (CD73): cDNA cloning and tissue distribution

Cited by 76 publications

References 26 publications

IFN-α Induced Adenosine Production on the Endothelium: A Mechanism Mediated by CD73 (Ecto-5′-Nucleotidase) Up-Regulation

IFN-α Induced Adenosine Production on the Endothelium: A Mechanism Mediated by CD73 (Ecto-5′-Nucleotidase) Up-Regulation

Cellular function and molecular structure of ecto-nucleotidases

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

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