Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10765072 | Biochemical and Biophysical Research Communications | 2010 | 6 Pages |
Abstract
Evidence exists that the adenosine receptor A2AR and the dopamine receptor D2R form constitutive heteromers in living cells. Mass spectrometry and pull-down data showed that an arginine-rich domain of the D2R third intracellular loop binds via electrostatic interactions to a specific motif of the A2AR C-terminal tail. It has been indicated that the phosphorylated serine 374 might represent an important residue in this motif. In the present study, it was found that a point mutation of serine 374 to alanine reduced the A2AR ability to interact with D2R. Also, this point mutation abolished the A2AR-mediated inhibition of both the D2R high affinity agonist binding and signaling. These results point to a key role of serine 374 in the A2AR-D2R interface. All together these results indicate that by targeting A2AR serine 374 it will be possible to allosterically modulate A2AR-D2R function, thus representing a new approach for therapeutically modulate D2R function.
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Authors
Dasiel O. Borroto-Escuela, Daniel Marcellino, Manuel Narvaez, Marc Flajolet, Nathaniel Heintz, Luigi Agnati, Francisco Ciruela, Kjell Fuxe,