ArticleProceedings of the National Academy of Sciences of the United States of America2008
Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 168 citations in OpenAlex.
- Trial
- Advances in Parathyroid Hormone-based medicines.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Review
- Loss-of-function GαScience signaling · 2025Article
- Characterization of the Two-Domain Peptide Binding Mechanism of the Human CGRP Receptor for CGRP and the Ultrahigh Affinity ssCGRP Variant.Biochemistry · 2025Article
- DimericeLife · 2025Article
- Genetic variants of accessory proteins and G proteins in human genetic disease.Critical reviews in clinical laboratory sciences · 2025Review
- Computational simulations of endocrine bone diseases related to pathological glandular PTH secretion using a multi-scale bone cell population model.Frontiers in bioengineering and biotechnology · 2025Article
- Beneath the surface: endosomal GPCR signaling.Trends in biochemical sciences · 2024Review
- Optimal Intermittent Administration Interval of Abaloparatide for Bone Morphogenetic Protein-Induced Bone Formation in a Rat Spinal Fusion Model.International journal of molecular sciences · 2024Article
- Parathyroid hormone-related protein as a potential prostate cancer biomarker: Promoting prostate cancer progression through upregulation of c-Met expression.Biomolecules & biomedicine · 2024Article
- Endosome positioning coordinates spatially selective GPCR signaling.Nature chemical biology · 2024Article
- Harnessing Aromatic-Histidine Interactions through Synergistic Backbone Extension and Side Chain Modification.Angewandte Chemie (International ed. in English) · 2023Article
- Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1.Acta pharmacologica Sinica · 2023Article
- Molecular Mechanisms of PTH/PTHrP Class B GPCR Signaling and Pharmacological Implications.Endocrine reviews · 2023Article
- Parathyroid Hormone-Related Protein/Parathyroid Hormone Receptor 1 Signaling in Cancer and Metastasis.Cancers · 2023Review
- Sex-Specific Differences in GJBMR plus · 2022Article
- Altered signaling at the PTH receptor via modified agonist contacts with the extracellular domain provides a path to prolonged agonism in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The why and how of sequential and combination therapy in osteoporosis. A review of the current evidence.Archives of endocrinology and metabolism · 2022Review
- Molecular insights into the distinct signaling duration for the peptide-induced PTH1R activation.Nature communications · 2022Article
- Endosomal parathyroid hormone receptor signaling.American journal of physiology. Cell physiology · 2022Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both the amino-terminal extracellular (N) domain, and transmembrane/extracellular loop, or juxtamembrane (J) regions of the receptor. Recently, we found that PTH(1-34), but not PTH-related protein, PTHrP(1-36), or M-PTH(1-14) (M = Ala/Aib(1),Aib(3),Gln(10),Har(11),Ala(12),Trp(14),Arg(19)), binds to the PTHR in a largely GTPgammaS-resistant fashion, suggesting selective binding to a novel, high-affinity conformation (R(0)), distinct from the GTPgammaS-sensitive conformation (RG). We examined the effects in vitro and in vivo of introducing the M substitutions, which enhance interaction to the J domain, into PTH analogs extended C-terminally to incorporate residues involved in the N domain interaction. As compared with PTH(1-34), M-PTH(1-28) and M-PTH(1-34) bound to R(0) with higher affinity, produced more sustained cAMP responses in cells, formed more stable complexes with the PTHR in FRET and subcellular localization assays, and induced more prolonged calcemic and phosphate responses in mice. Moreover, after 2 weeks of daily injection in mice, M-PTH(1-34) induced larger increases in trabecular bone volume and greater increases in cortical bone turnover, than did PTH(1-34). Thus, the putative R(0) PTHR conformation can form highly stable complexes with certain PTH ligand analogs and thereby mediate surprisingly prolonged signaling responses in bone and/or kidney PTH target cells. Controlling, via ligand analog design, the selectivity with which a PTH ligand binds to R(0), versus RG, may be a strategy for optimizing signaling duration time, and hence therapeutic efficacy, of PTHR agonist ligands.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.