The A2A-adenosine receptor: a GPCR with unique features?
Article first published online: 29 JAN 2009
2008 British Pharmacological Society
British Journal of Pharmacology
Special Issue: Special Issue: Life Sciences
Volume 153, Issue S1, pages S184–S190, March 2008
How to Cite
Zezula, J. and Freissmuth, M. (2008), The A2A-adenosine receptor: a GPCR with unique features?. British Journal of Pharmacology, 153: S184–S190. doi: 10.1038/sj.bjp.0707674
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received August 6, 2007, Revised September 7, 2007, Accepted December 13, 2007)
- A2A-adenosine receptor;
- MAP kinase;
- restricted collision coupling
The A2A-adenosine receptor is a prototypical Gs-coupled receptor. However, the A2A-receptor has several structural and functional characteristics that make it unique. In contrast to the classical model of collision coupling described for the β-adrenergic receptors, the A2A-receptor couples to adenylyl cyclase by restricted collision coupling and forms a tight complex with Gs. The mechanistic basis for this is not clear; restricted collision coupling may arise from the interaction of the receptor with additional proteins or due to the fact that G protein-coupling is confined to specialized membrane microdomains. The A2A-receptor has a long C-terminus (of >120 residues), which is for the most part dispensable for coupling to Gs. It was originally viewed as the docking site for kinases and the β-arrestin family to initiate receptor desensitization and endocytosis. The A2A-receptor is, however, fairly resistant to agonist-induced internalization. Recently, the C-terminus has also been appreciated as a binding site for several additional ‘accessory’ proteins. Established interaction partners include α-actinin, ARNO, USP4 and translin-associated protein-X. In addition, the A2A-receptor has also been reported to form a heteromeric complex with the D2-dopamine receptor and the metabotropic glutamate receptor-5. It is clear that (i) this list cannot be exhaustive and (ii) that all these proteins cannot bind simultaneously to the receptor. There must be rules of engagement, which allow the receptor to elicit different biological responses, which depend on the cellular context and the nature of the concomitant signal(s). Thus, the receptor may function as a coincidence detector and a signal integrator.
British Journal of Pharmacology (2008) 153, S184–S190; doi:10.1038/sj.bjp.0707674; published online 4 February 2008