ADENOSINE-DEAMINASE AFFECTS LIGAND-INDUCED SIGNALING BY INTERACTING WITH CELL-SURFACE ADENOSINE RECEPTORS

Adenosine deaminase (ADA) is not only a cytosolic enzyme but can be fo und 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 coprecipita tion experiments we show that A(1) adenosine receptor (A(1)R) is a sec ond ecto-ADA binding protein. Binding of ADA to A(1)R increased its af finity for the ligand thus suggesting that ADA was needed for an effec tive coupling between A(1)R and heterotrineric G proteins. This was co nfirmed by the fact that ASA, independently of its catalytic behaviour , enhanced the ligand-induced second messenger production via A(1)R. T hese findings demonstrate that, apart from the cleavage of adenosine, a further role of ecto-adenosine deaminase on the cell surface is to f acilitate the signal transduction via A(1)R.