Molecular basis for subtype-specific desensitization of inhibitory adenosine receptors. Analysis of a chimeric A1-A3 adenosine receptor
| Autor: | T M, Palmer, J L, Benovic, G L, Stiles |
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| Rok vydání: | 1996 |
| Předmět: |
Phosphopeptides
Adenosine Recombinant Fusion Proteins Molecular Sequence Data Palmitic Acid CHO Cells Palmitic Acids Transfection Epitopes Radioligand Assay Adenosine Triphosphate GTP-Binding Proteins Cricetinae Purinergic P1 Receptor Agonists Animals Humans Amino Acid Sequence Phosphorylation Sequence Tagged Sites Cell Membrane Colforsin Receptors Purinergic P1 Receptor Protein-Tyrosine Kinases Peptide Fragments Rats Kinetics Protein Processing Post-Translational |
| Zdroj: | The Journal of biological chemistry. 271(25) |
| ISSN: | 0021-9258 |
| Popis: | The differing effects of short-term agonist exposure on the two inhibitory adenosine receptor (AR) subtypes have been examined using Chinese hamster ovary cells stably expressing the hemagglutinin epitope-tagged human A1AR and rat A3AR. Under conditions in which exposure of transfected cells to 5 microM (-)-(R)-N6-(phenylisopropyl)adenosine resulted in the functional desensitization and phosphorylation of the A3AR, neither property was exhibited by the A1AR. However, a stably expressed chimeric A1-A3AR, termed A1CT3AR, in which the C-terminal domain of the A1AR distal to its predicted palmitoylation site was replaced by the corresponding region of the A3AR, was able to undergo functional desensitization and agonist-stimulated phosphorylation in a manner similar to that exhibited by the A3AR. Moreover, purified G-protein-coupled receptor kinases 2, 3, and 5 were each capable of enhancing the agonist-dependent phosphorylation of the A3AR and A1CT3AR in vitro. Taken together, these data demonstrate that the C-terminal domain of the A3AR distal to its predicted palmitoylation site is responsible for this receptor's ability to undergo a rapid agonist-dependent desensitization and are consistent with a model in which phosphorylation of the A3AR within this domain by one or more G-protein-coupled receptor kinases initiates the desensitization process. |
| Databáze: | OpenAIRE |
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