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 A 1 adenosine receptor (A 1 R) is a second ecto‐ADA binding protein. Binding of ADA to A 1 R increased its affinity for the ligand thus suggesting that ADA was needed for an effective coupling between A 1 R 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 A 1 R. 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 A 1 R.