ArticleThe Journal of biological chemistry2016
β2-Adrenergic Receptors Chaperone Trapped Bitter Taste Receptor 14 to the Cell Surface as a Heterodimer and Exert Unidirectional Desensitization of Taste Receptor Function.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- β2-Adrenergic Receptor Utilizes Distinct Interaction Interfaces to Selectively form Heterooligomers with a Subset of Bitter Taste Receptors.Biochemistry · 2025Article
- Article
- Chemosensory role of intracellular TAS2Rs, the activation of which triggers drug excretion by ABCB1 in cancer cells.Scientific reports · 2025Article
- A deadly taste: linking bitter taste receptors and apoptosis.Apoptosis : an international journal on programmed cell death · 2025Review
- TAS2R5 screening reveals biased agonism that fails to evoke internalization and downregulation resulting in attenuated desensitization.PloS one · 2025Article
- Intracellular TAS2Rs act as a gatekeeper for the excretion of harmful substances via ABCB1 in keratinocytes.FASEB bioAdvances · 2024Article
- Article
- Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14.Cell reports · 2023Article
- Investigating Carvedilol's Repurposing for the Treatment of Non-Small Cell Lung Cancer via Aldehyde Dehydrogenase Activity Modulation in the Presence of β-Adrenergic Agonists.Current issues in molecular biology · 2023Article
- Predicted structure and cell signaling of TAS2R14 reveal receptor hyper-flexibility for detecting diverse bitter tastes.iScience · 2023Article
- A Par3/LIM Kinase/Cofilin Pathway Mediates Human Airway Smooth Muscle Relaxation by TAS2R14.American journal of respiratory cell and molecular biology · 2023Article
- Cilia Stimulatory and Antibacterial Activities of T2R Bitter Taste Receptor Agonist Diphenhydramine: Insights into Repurposing Bitter Drugs for Nasal Infections.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The Effect of Beta Adrenoreceptor Blockers on Viability and Cell Colony Formation of Non-Small Cell Lung Cancer Cell Lines A549 and H1299.Molecules (Basel, Switzerland) · 2022Article
- Pharmacology of T2R Mediated Host-Microbe Interactions.Handbook of experimental pharmacology · 2022Article
- The bitter end: T2R bitter receptor agonists elevate nuclear calcium and induce apoptosis in non-ciliated airway epithelial cells.Cell calcium · 2022Article
- Identification and characterization of an atypical Gαs-biased βProceedings of the National Academy of Sciences of the United States of America · 2021Article
- A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors.Molecules (Basel, Switzerland) · 2020Article
- A Bitter Taste in Your Heart.Frontiers in physiology · 2020Review
- Differential long-term regulation of TAS2R14 by structurally distinct agonists.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Cholecystokinin, gastrin, cholecystokinin/gastrin receptors, and bitter taste receptor TAS2R14: trophoblast expression and signaling.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Bitter taste receptors (TAS2Rs) are G-protein-coupled receptors now recognized to be expressed on extraoral cells, including airway smooth muscle (ASM) where they evoke relaxation. TAS2Rs are difficult to express in heterologous systems, with most receptors being trapped intracellularly. We find, however, that co-expression of β2-adrenergic receptors (β2AR) in HEK-293T routes TAS2R14 to the cell surface by forming receptor heterodimers. Cell surface TAS2R14 expression was increased by ∼5-fold when β2AR was co-expressed. Heterodimer formation was shown by co-immunoprecipitation with tagged receptors, biomolecular fluorescence complementation, and merged confocal images. The dynamic nature of this interaction was shown by: a gene-dose relationship between transfected β2AR and TAS2R14 expression, enhanced (up to 3-fold) TAS2R14 agonist stimulation of [Ca(2+)]i with β2AR co-transfection, ∼53% decrease in [Ca(2+)]i signaling with shRNA knockdown of β2AR in H292 cells, and ∼60% loss of [Ca(2+)]i responsiveness in βAR knock-out mouse ASM. Once expressed on the surface, we detected unidirectional, conformation-dependent, interaction within the heterodimer, with β2AR activation rapidly uncoupling TAS2R14 function (∼65% desensitization). Cross-talk was independent of β2AR internalization and cAMP/PKA, and not accompanied by TAS2R14 internalization. With prolonged β-agonist exposure, TAS2R14 internalized, consistent with slow recycling of naked TAS2R14 in the absence of the heterodimeric milieu. In studies of ASM mechanics, rapid cross-talk was confirmed at the physiologic level, where relaxation from TAS2R14 agonist was decreased by ∼50% with β-agonist co-treatment. Thus the β2AR acts as a double-edged sword: increasing TAS2R14 cell surface expression, but when activated by β-agonist, partially offsetting the expression phenotype by direct receptor:receptor desensitization of TAS2R14 function.
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