Disease relevance of Entpd2

• Wild-type mouse hepatoma cells contain both constitutive and TCDD-inducible ecto-ATPase activity [1].
• Neuroblasts-glia interaction in tissue culture as evidenced by the study of ectoenzymes. Ecto-ATPase activity of mouse neuroblastoma cells [2].

High impact information on Entpd2

• Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation [3].
• In contrast, we now show that NTPDase2 (CD39L1, 75 kd), a preferential nucleoside triphosphatase, activates platelet aggregation by converting adenosine triphosphate (ATP) to ADP, the specific agonist of P2Y(1) and P2Y(12) receptors [3].
• Moreover, NTPDase2 represents a novel marker for microvascular pericytes [3].
• We have previously shown that the extracellular nucleoside triphosphate-hydrolyzing enzyme NTPDase2 is highly expressed in situ by stem/progenitor cells of the two neurogenic regions of the adult murine brain: the subventricular zone (type B cells) and the dentate gyrus of the hippocampus (residual radial glia) [4].
• A novel response to dioxin. Induction of ecto-ATPase gene expression [1].

Chemical compound and disease context of Entpd2

• Its predicted amino acid sequence suggests that the gene encodes an ecto-ATPase that contains multiple glycosylation sites, conserved cysteine residues, and apyrase conserved regions. cDNA expression experiments in mouse hepatoma cells confirm that the new gene encodes an ecto-ATPase [1].

Biological context of Entpd2

• In this context, NTPDase1 should abrogate platelet aggregation and recruitment in intact vessels by the conversion of ADP to adenosine monophosphate, while NTPDase2 expression would promote platelet microthrombus formation at sites of extravasation following vessel injury [3].
• Induction of ecto-ATPase gene expression by TCDD is direct and occurs at the transcriptional level [1].
• Furthermore, after mitosis, progenitor cells preferentially reveal an NTPDase2-positive phenotype [5].
• These results show that the ecto-ATPase of J774 cells does not mediate the effects of ATP on these cells; that ATP4- and not MgATP2- promotes 86Rb+ efflux from these cells; and that hydrolysis of ATP is not required to effect this change in membrane permeability [6].
• Tissue distribution of the ecto-ATPase showed that the highest levels of protein were expressed in muscle tissues (cardiac, skeletal, and smooth) and brain [7].

Anatomical context of Entpd2

• NTPDase1 has identity with CD39, a B lymphocyte activation marker, and hydrolyzes extracellular ATP and ADP to AMP within the vasculature, whereas NTPDase2/CD39L(ike)1 preferentially converts ATP to ADP outside of blood vessels [8].
• In contrast, NTPDase2 is expressed in Bowman's capsule, glomerular arterioles, adventitia of blood vessels, and pelvic wall [8].
• Our results identify the ecto-nucleotidase NTPDase2 and functional P2X receptors at hippocampal progenitor cells [5].
• In the hippocampus, the embryonic pattern of NTPDase2 expression mirrors that of the dentate migration of neuroblasts [5].
• We show that radial glia-like cells of the dentate gyrus express surface-located ATP-hydrolyzing activity and are immunopositive for NTPDase2 [5].

Associations of Entpd2 with chemical compounds

• We tested effects of known ATP-binding site-specific reagents fluorescein 5'-isothiocyanate (FITC) and 5'-fluorosulfonylbenzoyladenosine (FSBA) to find covalent modification procedures to be used in studies of functional role of ecto-ATPase [9].
• These findings suggest that J774 cells possess a plasma membrane receptor which binds ATP4-, AMP-PNP, and ATP-gamma-S, and that the ecto-ATPase limits the effects of ATP on these cells by hydrolyzing Mg-ATP2- [6].
• A Ca(2+)- or Mg(2+)-stimulated ecto-ATPase is thought to regulate the hydrolysis of extracellular ATP in nervous tissues [10].
• Suramin inhibited the growth of epimastigotes, suggesting a direct participation of ecto-ATPase activity in this process [11].
• In rat but not in mouse thymocytes the ecto-ATPase was inhibited in vitro by HgCl2, tricyclohexyltin chloride, di-n-butyltin dichloride, DDT, gamma HCH and desipramine [12].

Other interactions of Entpd2

• Double-immunolabeling revealed that NTPDase2 is associated with subpopulations of glial fibrillary acidic protein-, nestin- and doublecortin-positive radial cells [5].
• Our data therefore support a physiological role for NTPDase2 and other ectonucleotidases in the pancreas and salivary glands [13].
• To test whether the resistance of CTL to ATP is due to a high activity of ecto-ATPase, four independent assays of ATPase activity were utilized to demonstrate the presence and relatively high activity of the ecto-ATPase(s) on CTL surface [9].
• In agreement with this observation, NTPDase2 was located to the same membrane as GLAST, indicating that this enzyme is present in type I cells [14].

Analytical, diagnostic and therapeutic context of Entpd2

• Extended N-terminal sequence analysis of the immunopurified 66-kDa ecto-ATPase revealed some sequence homology with mouse lysosomal associated membrane protein [7].
• An increase of ecto-ATPase activity was also found in coculture of neuroblastoma cells with chick fibroblasts [2].

References