ArticleThe Journal of biological chemistry2010
By interacting with the C-terminal Phe of apelin, Phe255 and Trp259 in helix VI of the apelin receptor are critical for internalization.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 78 citations in OpenAlex.
- The chemokine receptor-like fourth extracellular loop of the apelin receptor differentially regulates apelin and elabela binding and signalling.British journal of pharmacology · 2026Article
- Apelin-APLNR pathway across development, inflammation, and vascular remodeling: an endothelial perspective.Experimental & molecular medicine · 2026Review
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- Click-Functionalized Cyanine Fluorogenic Dimers for Improved Detection of GPCRs: Application to Imaging of ApelinR in Living Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Metabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.Clinical science (London, England : 1979) · 2025Review
- Apelinergic System Affects Electrocardiographic Abnormalities Induced by Doxorubicin.Biomedicines · 2025Article
- Structure-function relationship and physiological role of apelin and its G protein coupled receptor.Biophysical reviews · 2023Review
- Expanding the apelin receptor pharmacological toolbox using novel fluorescent ligands.Frontiers in endocrinology · 2023Article
- Apelin-17 to diagnose idiopathic pulmonary arterial hypertension: A biomarker study.Frontiers in physiology · 2022Article
- Effective Use of Empirical Data for Virtual Screening against APJR GPCR Receptor.Molecules (Basel, Switzerland) · 2021Article
- Prolyl Carboxypeptidase Mediates the C-Terminal Cleavage of (Pyr)-Apelin-13 in Human Umbilical Vein and Aortic Endothelial Cells.International journal of molecular sciences · 2021Article
- A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia.Nature communications · 2021Article
- Apelin and Vasopressin: The Yin and Yang of Water Balance.Frontiers in endocrinology · 2021Review
- The Effects of Apelin and Elabela Ligands on Apelin Receptor Distinct Signaling Profiles.Frontiers in pharmacology · 2021Article
- Advances in therapeutic peptides targeting G protein-coupled receptors.Nature reviews. Drug discovery · 2020Review
- Cardiovascular response to small-molecule APJ activation.JCI insight · 2020Article
- The G Protein Biased Small Molecule Apelin Agonist CMF-019 is Disease Modifying in Endothelial Cell ApoptosisFrontiers in pharmacology · 2020Article
- Structure-guided discovery of a single-domain antibody agonist against human apelin receptor.Science advances · 2020Article
- Article
- The apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders.Annals of the New York Academy of Sciences · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apelin is the endogenous ligand of the orphan seven-transmembrane domain (TM) G protein-coupled receptor APJ. Apelin is involved in the regulation of body fluid homeostasis and cardiovascular functions. We previously showed the importance of the C-terminal Phe of apelin 17 (K17F) in the hypotensive activity of this peptide. Here, we show either by deleting the Phe residue (K16P) or by substituting it by an Ala (K17A), that it plays a crucial role in apelin receptor internalization but not in apelin binding or in Gα(i)-protein coupling. Then we built a homology three-dimensional model of the human apelin receptor using the cholecystokinin receptor-1 model as a template, and we subsequently docked K17F into the binding site. We visualized a hydrophobic cavity at the bottom of the binding pocket in which the C-terminal Phe of K17F was embedded by Trp(152) in TMIV and Trp(259) and Phe(255) in TMVI. Using molecular modeling and site-directed mutagenesis studies, we further showed that Phe(255) and Trp(259) are key residues in triggering receptor internalization without playing a role in apelin binding or in Gα(i)-protein coupling. These findings bring new insights into apelin receptor activation and show that Phe(255) and Trp(259), by interacting with the C-terminal Phe of the pyroglutamyl form of apelin 13 (pE13F) or K17F, are crucial for apelin receptor internalization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.