ArticleProceedings of the National Academy of Sciences of the United States of America2022
Functional modulation of PTH1R activation and signaling by RAMP2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Altered Intracellular Trafficking as a Mechanism for Prolonged Duration of G Protein-Coupled Receptor Activation.Journal of the American Chemical Society · 2026Article
- Structure-Encoded Location Biased Signaling in a Class B GPCR: Focus on the PTH Type 1 Receptor.Handbook of experimental pharmacology · 2026Review
- The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling.Science signaling · 2025Article
- Key Interaction Changes Determine the Activation Process of Human Parathyroid Hormone Type 1 Receptor.Journal of the American Chemical Society · 2025Article
- Extracellular bimolecular fluorescence complementation for investigating membrane protein dimerization: a proof of concept using class B GPCRs.Bioscience reports · 2024Article
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- ADAM19 cleaves the PTH receptor and associates with brachydactyly type E.Life science alliance · 2024Article
- Receptor activity-modifying protein modulation of parathyroid hormone-1 receptor function and signaling.Frontiers in pharmacology · 2024Article
- Molecular and Cellular Mechanisms of Osteoporosis.International journal of molecular sciences · 2023Review
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- New Insights into the Structure and Function of Class B1 GPCRs.Endocrine reviews · 2023Article
- Article
- Parathyroid Hormone-Related Protein/Parathyroid Hormone Receptor 1 Signaling in Cancer and Metastasis.Cancers · 2023Review
- Detecting and measuring of GPCR signaling - comparison of human induced pluripotent stem cells and immortal cell lines.Frontiers in endocrinology · 2023Review
- Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.Pharmacological reviews · 2023Review
- Endosomal parathyroid hormone receptor signaling.American journal of physiology. Cell physiology · 2022Review
- Proteolytic Cleavage of the Extracellular Domain Affects Signaling of Parathyroid Hormone 1 Receptor.Frontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptor-activity-modifying proteins (RAMPs) are ubiquitously expressed membrane proteins that associate with different G protein-coupled receptors (GPCRs), including the parathyroid hormone 1 receptor (PTH1R), a class B GPCR and an important modulator of mineral ion homeostasis and bone metabolism. However, it is unknown whether and how RAMP proteins may affect PTH1R function. Using different optical biosensors to measure the activation of PTH1R and its downstream signaling, we describe here that RAMP2 acts as a specific allosteric modulator of PTH1R, shifting PTH1R to a unique preactivated state that permits faster activation in a ligand-specific manner. Moreover, RAMP2 modulates PTH1R downstream signaling in an agonist-dependent manner, most notably increasing the PTH-mediated Gi3 signaling sensitivity. Additionally, RAMP2 increases both PTH- and PTHrP-triggered β-arrestin2 recruitment to PTH1R. Employing homology modeling, we describe the putative structural molecular basis underlying our functional findings. These data uncover a critical role of RAMPs in the activation and signaling of a GPCR that may provide a new venue for highly specific modulation of GPCR function and advanced drug design.
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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.