A novel Gαs-binding protein, Gas-2 like 2, facilitates the signaling of the A2A adenosine receptor.

The A2A adenosine receptor (A2AR) is a G-protein-coupled receptor that contains a long cytoplasmic carboxyl terminus (A2AR-C). We report here that Gas-2 like 2 (G2L2) is a new interacting partner of A2AR-C. The interaction between A2AR and G2L2 was verified by GST pull-down, co-immunoprecipitation, immunocytochemical staining, and fluorescence resonance energy transfer. Expression of G2L2 increased the intracellular cAMP content evoked by A2AR in an A2AR-C-dependent manner. Immunoprecipitation and pull-down assays demonstrated that G2L2 selectively bound to A2AR-C and the inactive form of Gαs to facilitate the recruitment of the trimeric G protein complex to the proximal position of A2AR for efficient activation. Collectively, G2L2 is a new effector that controls the action of A2AR by modulating its ability to regulate the Gαs-mediated cAMP contents.