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The PTH Receptorsome and Transduction Pathways

  • Thomas J. GardellaEmail author
Chapter

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.

Keywords

Parathyroid hormone Receptor interactions Two-site binding mechanism Ligand binding GPCR structure 

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Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  1. 1.Endocrine UnitMassachusetts General Hospital, Harvard Medical SchoolBostonUSA

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