Volume 7 Supplement 2

13th Scientific Symposium of the Austrian Pharmacological Society (APHAR). Joint Meeting with the Austrian Society of Toxicology (ASTOX) and the Hungarian Society for Experimental and Clinical Pharmacology (MFT)

Open Access

Mapping the binding sites for accessory proteins on the A2A adenosine receptor

  • Ivana Ostrouska1,
  • Ingrid Gsandtner1,
  • Halyna Pankevych1,
  • Christian Nanoff1 and
  • Oliver Kudlacek1Email author
BMC Pharmacology20077(Suppl 2):A19


Published: 14 November 2007

Among the four receptors for the purine nucleoside adenosine the A2A receptor subtype is the only one with an extended cytoplasmic domain and this is due to a remarkably long carboxyl terminal tail (C-tail). We have previously identified from an adult human brain cDNA library potential interaction partners which bind to the receptor C-tail and suggest that they impinge on receptor biology. (i) ARNO, the activator of the small GTP-binding protein ARF6, was shown to propagate sustained receptor signalling to ERK (extracellular signal regulated kinase); (ii) the ubiquitin-splitting protease USP4 controls receptor turnover; (iii) SAP (synapse-associated protein) 102 may form an anchor localizing the receptor in nerve cells. While ARNO binds to the membrane proximal portion, USP4 and SAP102 recognize more distal segments of the C-tail. In the case of SAP102 the recognition sequence could be narrowed down to a stretch of five amino acid residues (DVELL) which is conserved between species. A receptor where the DVELL sequence was changed to RVRAA has been characterized upon stable transfection of HEK293 cells (which express SAP102). Surface expression, radioligand binding and receptor-dependent stimulation of the effector adenylyl cyclase were similar to the wild type. In contrast, the agonist-dependent activation of ERK was attenuated in cells stably expressing the mutant receptor. Hence, SAP102 may be necessary to establish a signalling complex including ERK and the receptor as has been previously observed for the NMDA receptor in nerve cells.

Authors’ Affiliations

Department of Pharmacology, Medical University of Vienna


© Ostrouska et al; licensee BioMed Central Ltd. 2007

This article is published under license to BioMed Central Ltd.