QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Related Article All Versions of this Article: mol.106.026757v1 70/2/447    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Related articles in MolPharm Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gsandtner, I. Articles by Freissmuth, M. Search for Related Content PubMed PubMed Citation Articles by Gsandtner, I. Articles by Freissmuth, M.

Perspective

A Tail of Two Signals: The C Terminus of the A_2A-Adenosine Receptor Recruits Alternative Signaling Pathways

Institute of Pharmacology, Center of Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria

G protein-coupled receptors are endowed with carboxyl termini that vary greatly in length and sequence. In most instances, the distal portion of the C terminus is dispensable for G protein coupling. This is also true for the A_2A-adenosine receptor, where the last 100 amino acids are of very modest relevance to G_s coupling. The C terminus was originally viewed mainly as the docking site for regulatory proteins of the -arrestin family. These -arrestins bind to residues that have been phosphorylated by specialized kinases (G protein-coupled receptor kinases) and thereby initiate receptor desensitization and endocytosis. More recently, it has become clear that many additional "accessory" proteins bind to C termini of G protein-coupled receptors. The article by Sun et al. (p. 454) in the current issue of Molecular Pharmacology identifies translin-associated protein-X as yet another interaction partner of the A_2A receptor; translin-associated protein allows the A_2A receptor to impinge on the signaling mechanisms by which p53 regulates neuronal differentiation, but the underlying signaling pathways are uncharted territory. With a list of five known interaction partners, the C terminus of the A_2A receptor becomes a crowded place. Hence, there must be rules that regulate the interaction. This allows the C terminus to act as coincidence detector and as signal integrator. Despite our ignorance about the precise mechanisms, the article has exciting implications: the gene encoding for translin-associated protein-X maps to a locus implicated in some forms of schizophrenia; A_2A receptor agonists are candidate drugs for the treatment of schizophrenic symptoms. It is of obvious interest to explore a possible link.

Received for publication May 17, 2006.

Accepted for publication May 17, 2006.

Address correspondence to: Michael Freissmuth, Institute of Pharmacology, Medical University of Vienna, Währinger Str. 13a, A-1090 Vienna, Austria. E-mail: michael.freissmuth{at}meduniwien.ac.at

Related articles in MolPharm:

Rescue of p53 Blockage by the A_2A Adenosine Receptor via a Novel Interacting Protein, Translin-Associated Protein X

Chung-Nan Sun, Hsiao-Chun Cheng, Jui-ling Chou, Shen-Yang Lee, Ya-Wen Lin, Hsing-Lin Lai, Hui-Mei Chen, and Yijuang Chern
MolPharm 2006 70: 454-466. [Abstract] [Full Text]  

This article has been cited by other articles:

				C. van der Putten, E. A. Zuiderwijk-Sick, L. van Straalen, E. D. de Geus, L. A. Boven, I. Kondova, A. P. IJzerman, and J. J. Bajramovic Differential Expression of Adenosine A3 Receptors Controls Adenosine A2A Receptor-Mediated Inhibition of TLR Responses in Microglia J. Immunol., June 15, 2009; 182(12): 7603 - 7612. [Abstract] [Full Text] [PDF]

				C. Charalambous, I. Gsandtner, S. Keuerleber, L. Milan-Lobo, O. Kudlacek, M. Freissmuth, and J. Zezula Restricted Collision Coupling of the A2A Receptor Revisited: EVIDENCE FOR PHYSICAL SEPARATION OF TWO SIGNALING CASCADES J. Biol. Chem., April 4, 2008; 283(14): 9276 - 9288. [Abstract] [Full Text] [PDF]