E-type-ATP(D)ases

A hydrolysis of extracellular ATP, catalyzed by the ecto-ATP(D)ase of intact vascular tissue.
Segments of (rat) mesenteric artery were incubated in physiological salt solution at 370C containing 1 mM of ATP.

E-type-ATP(D) ases are ubiquitous enzymes with a very high turn-over-number (104s-1) (1-3). E-type-ATP(D)ases from microorganisms, plants and animal tissues have been cloned, and the same conserved sequences were found throughout the phylogenetic three, i.e. most E-type-ATP(D)ases belong to the same gene-family (4).

Most E-type-ATP(D)ases are ecto-ATP(D)ases which hydrolyze ATP and other nucleotides on the outside of the cell membrane. Within recent years the transmitter function and the important multiple physiological effects of extracellular nucleotides have been established, and as a result, interest in ecto-ATP(D)ases was considerably increased, since ecto-ATP(D)ases are supposed to play a crucial role in regulating the concentration of the nucleotide agonists around their receptors, the purinoceptors. As part of this key system in signal transduction the ecto-ATP(D)ase of the vascular system (CD39) has pronounced medical interest in connection to thromboregulation (cf Figur). In malignancy the function of the ecto-ATP(D)ase may be to enable the tumor cell to escape immunological recognition (5), and in microorganisms the enzyme may be part of the mechanism that enables the parasite lacking purine synthesis to survive on host cell nucleotides.

We produced monoclonal antibodies against the vascular enzyme and a series of polyclonal antibodies against conserved sequences. These antibodies are used to investigate structure and function of hepatic ecto-ATP(D)ase (in collaboration with P.Schwarzbaum, Buenos Aires) and ecto-ATP(D)ases of microorganisms that proliferate within the host cell (in collaboration with J.Kristiansen, Sønderborg). Ecto-ATP(D)ase inhibitor DEPC is used (in collaboration with K.Dzhandzhugazyan, Kræftens Bekæmpelse, Copenhagen) to study the possible role of ecto-ATP(D)ases in cancer cell escape from immunological control.

 

  1. Plesner,L. (1995) "Ecto-ATPaser, Identitet og funktion", International Review of Cytology, 158, 141-214.
  2. "Ecto-ATPases: Recent progress on Structure and Function" (1997). (L.Plesner, T.L.Kirley, and A.F.Knowles eds.) Plenum Publishing Corporation, New York.
  3. Plesner,L. (1997) Ecto-ATPase Data-base/Homepage: http://www.ecto.au.dk
  4. Nagy, A.K., Knowles, A.F. and Nagami, G. (1998) Molecular cloning of the chicken oviduct ecto-ATP-diphosphohydrolase. J.Biol.Chem. 273, 16043-16049
  5. Dzhandzhugazyan, K. et al. (1998) Ecto-ATP-diphosphohydrolase (CD39 is overexpressed in differentiated human melanomas FEBS Letters, 430:227-230.

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