title: Adenosine deaminase affects ligand-induced signalling by interacting with cell surface adenosine receptors.
abstract: Adenosine deaminase (ADA) is not only a cytosolic enzyme but can be found as an ecto-enzyme. At the plasma membrane, an adenosine deaminase binding protein (CD26, also known as dipeptidylpeptidase IV) has been identified but the functional role of this ADA/CD26 complex is unclear. Here by confocal microscopy, affinity chromatography and coprecipitation experiments we show that A1 adenosine receptor (A1R) is a second ecto-ADA binding protein. Binding of ADA to A1R increased its affinity for the ligand thus suggesting that ADA was needed for an effective coupling between A1R and heterotrimeric G proteins. This was confirmed by the fact that ASA, independently of its catalytic behaviour, enhanced the ligand-induced second messenger production via A1R. These findings demonstrate that, apart from the cleavage of adenosine, a further role of ecto-adenosine deaminase on the cell surface is to facilitate the signal transduction via A1R.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Química, Universitat de Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Ciruela
authors.forename: C
authors.initials: C
authors.lastname: Saura
authors.forename: E I
authors.initials: EI
authors.lastname: Canela
authors.forename: J
authors.initials: J
authors.lastname: Mallol
authors.forename: C
authors.initials: C
authors.lastname: Lluis
authors.forename: R
authors.initials: R
authors.lastname: Franco
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D002846:Chromatography, Affinity; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000378:metabolism; D007163:Immunosorbent Techniques; D010660:Phenylisopropyladenosine / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction; D014316:Tritium
chemical_list: D018047:Receptors, Purinergic P1; D014316:Tritium; D010660:Phenylisopropyladenosine; D018819:Dipeptidyl Peptidase 4; D000243:Adenosine Deaminase; D019204:GTP-Binding Proteins