ArticleScience signaling2021
Spatial bias in cAMP generation determines biological responses to PTH type 1 receptor activation.
Erratum issuedOpen access · greenAbstract read
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Article in Science signaling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers.
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50citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
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50 citing papers in PubMed, 77 citations in OpenAlex.
- Spatial control of parathyroid hormone receptor-1 signaling dictates ligand-specific biological outcomes.Signal transduction and targeted therapy · 2026Article
- Spatiotemporal modeling of GPCR signaling: The role of endosomal dynamics and receptor recycling.PLoS computational biology · 2026Article
- Inhibitory probes for spatiotemporal analysis of GαNature chemical biology · 2026Article
- Elucidating the neuropathological and molecular heterogeneity of amyloid beta and tau in Alzheimer's disease through machine learning and transcriptomic integration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- The working lives of neuronal 5-HTRSC chemical biology · 2026Review
- G-protein regulatory network governs receptor internalization dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Altered Intracellular Trafficking as a Mechanism for Prolonged Duration of G Protein-Coupled Receptor Activation.Journal of the American Chemical Society · 2026Article
- Structural basis of PTH1R-β-arrestin core engagement reveals design principles for G-protein-biased therapeutics.Nature structural & molecular biology · 2026Article
- Core conformation of arrestin coupling to parathyroid hormone type 1 receptor.Nature communications · 2026Article
- GPCR-selective effects of endocytosis on cellular signaling through the cAMP/PKA cascade.The Journal of biological chemistry · 2026Article
- Conformational biosensors delineate endosomal G protein regulation by GPCRs.Nature communications · 2026Article
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Spatially diffuse cAMP signalling with oppositely biased GLP-1 receptor agonists in β-cells despite differences in receptor localisation.Molecular metabolism · 2026Article
- Structure-Encoded Location Biased Signaling in a Class B GPCR: Focus on the PTH Type 1 Receptor.Handbook of experimental pharmacology · 2026Review
- Chemical biology approaches to resolve the subcellular GPCR signaling landscape.Nature chemical biology · 2025Review
- Atenolol, alone or in combination with PTH, has a modest effect on bone in female C57BL/6J mice.JBMR plus · 2025Article
- Prolonging parathyroid hormone analog action in vitro and in vivo through peptide lipidation.Nature communications · 2025Article
- Prolonged signaling of backbone-modified glucagon-like peptide-Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Intersection of GPCR trafficking and cAMP signaling at endomembranes.The Journal of cell biology · 2025Review
- Allosteric mechanism in the distinctive coupling of GProceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 4 institutions in 1 country.
Alex D WhiteDepartment of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0003-2180-2136
Karina A PeñaDepartment of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0001-6401-5269
Lisa J ClarkDepartment of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0003-0484-4596
Christian Santa MariaEndocrine Research Unit, Department of Veterans Affairs Medical Center, and University of California, San Francisco, CA 94158, USA.ORCID 0000-0002-7842-1740
Shi LiuDepartment of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.ORCID 0000-0002-9113-6207
Frédéric G Jean-AlphonseDepartment of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0002-7380-5825
Ji Young LeeDepartment of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.ORCID 0000-0002-1491-6963
Saifei LeiDepartment of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0003-2885-8423
Zhiqiang ChengEndocrine Research Unit, Department of Veterans Affairs Medical Center, and University of California, San Francisco, CA 94158, USA.
Chia-Ling TuEndocrine Research Unit, Department of Veterans Affairs Medical Center, and University of California, San Francisco, CA 94158, USA.
Fei FangDepartment of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0003-0829-9871
Nicholas SzetoEndocrine Research Unit, Department of Veterans Affairs Medical Center, and University of California, San Francisco, CA 94158, USA.
Thomas J GardellaEndocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Kunhong XiaoDepartment of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0002-1069-1226
Samuel H GellmanDepartment of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.ORCID 0000-0001-5617-0058
Ivet BaharDepartment of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.ORCID 0000-0001-9959-4176
Ieva SutkeviciuteDepartment of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0002-2168-3344
Wenhan ChangEndocrine Research Unit, Department of Veterans Affairs Medical Center, and University of California, San Francisco, CA 94158, USA.
Jean-Pierre VilardagaDepartment of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.ORCID 0000-0002-1217-1435
University of Pittsburgh · USSan Francisco VA Medical Center · USUniversity of Wisconsin–Madison · USHarvard University · US
Funding
Tissue Phenotyping CoreP01DK011794 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI GARDELLA, THOMAS J · 1986 to 2023
$44.4MTrainingP41GM103712 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SEJNOWSKI, TERRENCE J · 2012 to 2021
$16.3MUCSF INTEGRATED DDS-PHD TRAINING PROGRAMT32DE007306 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Yukiko Nakano · 1996 to 2026
$15.4MUCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3MProtein Recognition by Peptidic FoldamersR01GM056414 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GELLMAN, SAMUEL H. · 1997 to 2023
$6.5MStructure and function of PTH class B GPCRR01DK116780 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ivet Bahar, Jean-Pierre Vilardaga · 2018 to 2026
$4.2MSkeletal Phenotyping CoreP30AR066261 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DIVIETI PAJEVIC, PAOLA · 2014 to 2018
$3.5MUCSF Core Center for Musculoskeletal Biology and MedicineP30AR066262 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MAJUMDAR, SHARMILA · 2014 to 2018
$3.0MToward a Deeper Understanding of Allostery and Allotargeting by Computational ApproachesR01GM139297 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ivet Bahar · 2021 to 2026
$2.8MFunctional Polarity of PTH Receptor Signaling: Cellular and Molecular MechanismsR01DK111427 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FRIEDMAN, PETER A, VILARDAGA, JEAN-PIERRE · 2017 to 2020
$2.4MRegulation of Parathyroid Functions By G-Protein Coupled ReceptorsR01DK122259 · NIDDK · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI CHANG, WENHAN, VILARDAGA, JEAN-PIERRE · 2019 to 2023
$2.2MCombined PTH and Calcimimetic Therapy and Its Mechanisms for OsteoanabolismR01AR067291 · NIAMS · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI CHANG, WENHAN · 2015 to 2019
$1.7MBLRD VA I01 BX003453BLRD VA I01 BX005851BLRD VA IK6 BX004835NCI NIH HHS T32 CA009120NIAMS NIH HHS F31 AR074843NIAMS NIH HHS P30 AR066261NIAMS NIH HHS P30 AR066262NIAMS NIH HHS R01 AR067291NIA NIH HHS R21 AG070721NIDCR NIH HHS T32 DE007306NIDDK NIH HHS P01 DK011794NIDDK NIH HHS R01 DK111427NIDDK NIH HHS R01 DK116780NIDDK NIH HHS R01 DK122259NIGMS NIH HHS P41 GM103712NIGMS NIH HHS R01 GM056414NIGMS NIH HHS R01 GM139297NIGMS NIH HHS T32 GM088119
Abstract
The parathyroid hormone (PTH) type 1 receptor (PTHR) is a class B G protein–coupled receptor (GPCR) that regulates mineral ion, vitamin D, and bone homeostasis. Activation of the PTHR by PTH induces both transient cell surface and sustained endosomal cAMP production. To address whether the spatial (location) or temporal (duration) dimension of PTHR-induced cAMP encodes distinct biological outcomes, we engineered a biased PTHR ligand (PTH
Indexed as
Parathyroid HormoneReceptors, Parathyroid HormoneCyclic AMPCyclic AMPParathyroid HormoneReceptors, Parathyroid Hormone
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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.