ArticleThe Journal of biological chemistry2014
Identification of serine 348 on the apelin receptor as a novel regulatory phosphorylation site in apelin-13-induced G protein-independent biased signaling.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 59 citations in OpenAlex.
- Apelin Receptor Homodimerisation Inhibits Hippocampal Neuronal Autophagy via G Protein-Dependent Signalling in Vascular Dementia.Molecular neurobiology · 2025Article
- Structure-function relationship and physiological role of apelin and its G protein coupled receptor.Biophysical reviews · 2023Review
- Intrinsically disordered proteins and proteins with intrinsically disordered regions in neurodegenerative diseases.Biophysical reviews · 2022Review
- The beneficial roles of apelin-13/APJ system in cerebral ischemia: Pathogenesis and therapeutic strategies.Frontiers in pharmacology · 2022Review
- Constitutive signal bias mediated by the human GHRHR splice variant 1.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Role of Apelin/Apelin Receptor in Energy Metabolism and Water Homeostasis: A Comprehensive Narrative Review.Frontiers in physiology · 2021Review
- 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
- Biased signaling in naturally occurring mutations of G protein-coupled receptors associated with diverse human diseases.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- 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 apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders.Annals of the New York Academy of Sciences · 2019Review
- International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand.Pharmacological reviews · 2019Review
- Biased Signaling and Allosteric Modulation at the FSHR.Frontiers in endocrinology · 2019Review
- Biased signalling: from simple switches to allosteric microprocessors.Nature reviews. Drug discovery · 2018Review
- β-Arrestin Based Receptor Signaling Paradigms: Potential Therapeutic Targets for Complex Age-Related Disorders.Frontiers in pharmacology · 2018Review
- Characterization of the Apelin/Elabela Receptors (APLNR) in Chickens, Turtles, and Zebrafish: Identification of a Novel Apelin-Specific Receptor in Teleosts.Frontiers in endocrinology · 2018Article
- Apelinergic System Structure and Function.Comprehensive Physiology · 2017Review
- C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways.Molecular pharmacology · 2017Article
- Apelin receptor homodimer-oligomers revealed by single-molecule imaging and novel G protein-dependent signaling.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphorylation plays vital roles in the regulation of G protein-coupled receptor (GPCR) functions. The apelin and apelin receptor (APJ) system is involved in the regulation of cardiovascular function and central control of body homeostasis. Here, using tandem mass spectrometry, we first identified phosphorylated serine residues in the C terminus of APJ. To determine the role of phosphorylation sites in APJ-mediated G protein-dependent and -independent signaling and function, we induced a mutation in the C-terminal serine residues and examined their effects on the interaction between APJ with G protein or GRK/β-arrestin and their downstream signaling. Mutation of serine 348 led to an elimination of both GRK and β-arrestin recruitment to APJ induced by apelin-13. Moreover, APJ internalization and G protein-independent ERK signaling were also abolished by point mutation at serine 348. In contrast, this mutant at serine residues had no demonstrable impact on apelin-13-induced G protein activation and its intracellular signaling. These findings suggest that mutation of serine 348 resulted in inactive GRK/β-arrestin. However, there was no change in the active G protein thus, APJ conformation was biased. These results provide important information on the molecular interplay and impact of the APJ function, which may be extrapolated to design novel drugs for cardiac hypertrophy based on this biased signal pathway.
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