ArticleBritish journal of pharmacology2002
Constitutive activation of the neurotensin receptor 1 by mutation of Phe(358) in Helix seven.
Article in British journal of pharmacology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 35 citations in OpenAlex.
- Neurotensin and Alcohol Use Disorders: Towards a Pharmacological Treatment.International journal of molecular sciences · 2023Review
- Ligands selectively tune the local and global motions of neurotensin receptor 1 (NTSCell reports · 2023Article
- Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism.Science advances · 2021Article
- Dynamic tuneable G protein-coupled receptor monomer-dimer populations.Nature communications · 2018Article
- Structure and dynamics of a constitutively active neurotensin receptor.Scientific reports · 2016Article
- Rapid Computational Prediction of Thermostabilizing Mutations for G Protein-Coupled Receptors.Journal of chemical theory and computation · 2014Article
- Minireview: More than just a hammer: ligand "bias" and pharmaceutical discovery.Molecular endocrinology (Baltimore, Md.) · 2014Review
- Optimising the combination of thermostabilising mutations in the neurotensin receptor for structure determination.Biochimica et biophysica acta · 2013Article
- Structure of the agonist-bound neurotensin receptor.Nature · 2012Article
- Thermostabilization of the neurotensin receptor NTS1.Journal of molecular biology · 2009Article
- Engineering G protein-coupled receptor expression in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Directed evolution of a G protein-coupled receptor for expression, stability, and binding selectivity.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors.Molecular biotechnology · 2008Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. The neurotensin receptor 1, NTS1, is a G protein-coupled receptor with seven transmembrane domains (TM) that mediates most of the known effects of the neuropeptide. Our previous studies have pointed to extracellular loop 3 and adjacent TM7 as being potentially involved in agonist-induced activation of the NTS1. 2. Here we investigated residues in these domains that might be involved in transconformational activation of the rat NTS1. Single amino acid mutated receptors were expressed in COS cells and inositol phosphate (IP) and cyclic AMP productions were studied. 3. The F358A mutation in TM7 resulted in a time- and receptor concentration-dependent increase in spontaneous IP production. At expression levels of 12 pmol mg(-1), agonist-independent IP production was increased 10 fold over basal for the F358A mutant receptor whereas the wild type NTS1 exhibited virtually no spontaneous activity at expression levels of 7.5 pmol mg(-1). 4. Neurotensin remained agonist on the F358A mutant receptor with a maximal effect that amounted to greater than twice basal IP levels. SR 48692 was inverse agonist at the mutant receptor, reversing IP production almost back to the levels measured in wild type NTS1-transfected cells. 5. Cyclic AMP production was not constitutively activated with the F358A mutant receptor but was stimulated by neurotensin with the same concentration dependence as that observed with the wild type NTS1. 6. This is the first report, to our knowledge, of a constitutively active mutant of the NTS1. The data are consistent with TM7 being involved in the transconformational changes that lead to agonist-induced coupling of the NTS1 to Gq.
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