Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells.
Adenosine deaminase (ADA) is an enzyme of the purine metabolism that has been largely considered to be cytosolic. Recently, it has been demonstrated that the enzyme appears on the surface of lymphocytes where it interacts with the T-cell activation antigen CD26. ADA also appears on the surface of nonlymphoid cells anchored to adenosine A1 receptors. Here it is demonstrated that cell surface ADA in ADA+/CD26- T lymphocytes anchors to adenosine receptors of the A2B subtype (A2BR). An interaction between A2BR and cell surface ADA has been demonstrated in transfected Chinese hamster ovary cells and Jurkat J32 T lymphocytes. This has been proved by coimmunoprecipitation, binding of exogenous ADA to A2BR+ cells, and coimmunolocalization. The specificity of the interaction has also been demonstrated by the lack of interaction with other members of the G protein-coupled receptor superfamily. Binding of ADA to A2BR increases the affinity of the agonist 5'-N-ethylcarboxamidoadenosine and cAMP production. This effect occurs even when ADA devoid of enzyme activity is used. Therefore, in lymphocytes, cell surface ADA, apart from degrading extracellular adenosine, regulates those actions of adenosine that are mediated via adenosine receptors of the A2B subtype.
Herrera
C
C
Department of Biochemistry and Molecular Biology, Faculty of Chemistry, University of Barcelona, Barcelona, Spain.
Casadó
V
V
Ciruela
F
F
Schofield
P
P
Mallol
J
J
Lluis
C
C
Franco
R
R
D000243:Adenosine Deaminase / Q000096:biosynthesis / Q000378:metabolism*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D018613:Microscopy, Confocal; D011233:Precipitin Tests; D058906:Purinergic P1 Receptor Agonists; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D014162:Transfection
D058906:Purinergic P1 Receptor Agonists; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D000243:Adenosine Deaminase