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The PTH Receptorsome and Transduction Pathways

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Hypoparathyroidism

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Abstract

The parathyroid hormone receptor (PTHR1) mediates the actions of PTH in bone and kidney cells. The PTHR1 is a seven transmembrane domain-containing, G protein-coupled receptor (GPCR) and is a member of the “family B” subgroup of GPCRs that bind peptide hormones. PTH interacts with the PTHR1 via a “two-site” mechanism, by which the C-terminal portion of the bioactive PTH(1–34) peptide interacts with the amino-terminal extracellular domain (ECD) of the PTHR1 to establish binding affinity and the N-terminal portion of the ligand interacts with the transmembrane domain (TMD) region of the receptor to induce receptor activation and signal transduction. The activated PTHR1 couples strongly to the cAMP/PKA signaling pathway, but can also couple to other pathways, including the PLC/IP3/PKC and ERK-1/2 pathways. The activated PTHR1 is rapidly phosphorylated on its C-terminal tail and then internalizes via a β-arrestin-mediated mechanism leading to signal termination. Novel PTH ligands have been developed, however, that mediate prolonged signaling, possibly from an internalized endosomal domain. Such PTH analogs may offer new approaches for treating hypoparathyroidism.

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Authors and Affiliations

  1. Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Thier 10, 50 Blossom Street, Boston, MA, 02114, USA

    Thomas J. Gardella PhD

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  1. Thomas J. Gardella PhD
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Correspondence to Thomas J. Gardella PhD .

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Editors and Affiliations

  1. Unit of Metabolic and Bone Diseases, University of Florence, Florence, Italy

    Maria Luisa Brandi

  2. Division of Endocrinology, Diabetes and Hypertension, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts, USA

    Edward Meigs Brown

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Gardella, T.J. (2015). The PTH Receptorsome and Transduction Pathways. In: Brandi, M., Brown, E. (eds) Hypoparathyroidism. Springer, Milano. https://doi.org/10.1007/978-88-470-5376-2_9

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  • DOI: https://doi.org/10.1007/978-88-470-5376-2_9

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  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-5375-5

  • Online ISBN: 978-88-470-5376-2

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