Ciruela F, Saura C, Canela E I, Mallol J, Lluis C, Franco R
Departament de Bioquímica i Biologia Molecular, Facultat de Química, Universitat de Barcelona, Spain.
FEBS Lett. 1996 Feb 19;380(3):219-23. doi: 10.1016/0014-5793(96)00023-3.
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.
腺苷脱氨酶（ADA）不仅是一种胞质酶，也可作为一种胞外酶被发现。在质膜上，已鉴定出一种腺苷脱氨酶结合蛋白（CD26，也称为二肽基肽酶IV），但这种ADA/CD26复合物的功能作用尚不清楚。在此，通过共聚焦显微镜、亲和色谱和共沉淀实验，我们表明A1腺苷受体（A1R）是另一种胞外ADA结合蛋白。ADA与A1R的结合增加了其对配体的亲和力，因此表明ADA是A1R与异源三聚体G蛋白有效偶联所必需的。这一点通过以下事实得到证实：阿司匹林（ASA）与其催化行为无关，增强了通过A1R的配体诱导的第二信使产生。这些发现表明，除了腺苷的裂解外，细胞表面胞外腺苷脱氨酶的另一个作用是促进通过A1R的信号转导。
