ArticleBiochemical and biophysical research communications2001
Constitutive activation of A(3) adenosine receptors by site-directed mutagenesis.
Article in Biochemical and biophysical research communications, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 39 citations in OpenAlex.
- Efficient G protein coupling is not required for agonist-mediated internalization and membrane reorganization of the adenosine AFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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- Molecular Dynamics Simulations of the Allosteric Modulation of the Adenosine A2A Receptor by a Mini-G Protein.Scientific reports · 2019Article
- Intracellular Receptor Modulation: Novel Approach to Target GPCRs.Trends in pharmacological sciences · 2018Review
- Structural Probing and Molecular Modeling of the A₃ Adenosine Receptor: A Focus on Agonist Binding.Molecules (Basel, Switzerland) · 2017Review
- Selectivity in the Use of Gi/o Proteins Is Determined by the DRF Motif in CXCR6 and Is Cell-Type Specific.Molecular pharmacology · 2015Article
- A yeast screening method to decipher the interaction between the adenosine A2B receptor and the C-terminus of different G protein α-subunits.Purinergic signalling · 2014Article
- Functional analysis of the murine cytomegalovirus chemokine receptor homologue M33: ablation of constitutive signaling is associated with an attenuated phenotype in vivo.Journal of virology · 2008Article
- Common structural requirements for heptahelical domain function in class A and class C G protein-coupled receptors.The Journal of biological chemistry · 2007Article
- Lysophosphatidylcholine-induced surface redistribution regulates signaling of the murine G protein-coupled receptor G2A.Molecular biology of the cell · 2005Article
- Purine receptors: GPCR structure and agonist design.Molecular interventions · 2004Article
- Engineering of ADrug development research · 2003Article
- Identification by site-directed mutagenesis of residues involved in ligand recognition and activation of the human A3 adenosine receptor.The Journal of biological chemistry · 2002Article
- 2-Chloro-N(6)-cyclopentyladenosine, adenosine A(1) receptor agonist, antagonizes the adenosine A(3) receptor.European journal of pharmacology · 2002Article
- Neoceptor concept based on molecular complementarity in GPCRs: a mutant adenosine A(3) receptor with selectively enhanced affinity for amine-modified nucleosides.Journal of medicinal chemistry · 2001Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The objective of this study was to create constitutively active mutant human A(3) adenosine receptors (ARs) using single amino acid replacements, based on findings from other G protein-coupled receptors. A(3) ARs mutated in transmembrane helical domains (TMs) 1, 3, 6, and 7 were expressed in COS-7 cells and subjected to agonist radioligand binding and phospholipase C (PLC) and adenylyl cyclase (AC) assays. Three mutant receptors, A229E in TM6 and R108A and R108K in the DRY motif of TM3, were found to be constitutively active in both functional assays. The potency of the A(3) agonist Cl-IB-MECA (1-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide) in PLC activation was enhanced by at least an order of magnitude over wild type (EC(50) 951 nM) in R108A and A229E mutant receptors. Cl-IB-MECA was much less potent (>10-fold) in C88F, Y109F, and Y282F and mutants or inactive following double mutation of the DRY motif. The degree of constitutive activation was more pronounced for the AC signaling pathway than for the PLC signaling pathway. The results indicated that specific locations within the TMs proximal to the cytosolic region were responsible for constraining the receptor in a G protein-uncoupled conformation.
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