Non-canonical Signaling of the PTH Receptor

Overview

Journal Trends Pharmacol Sci

Specialty Pharmacology

Date 2012 Jun 20

PMID 22709554

Citations 28

Authors

Jean-Pierre Vilardaga

Thomas J Gardella

Vanessa L Wehbi

Timothy N Feinstein

Affiliations

Soon will be listed here.

Abstract

The classical model of arrestin-mediated desensitization of cell-surface G-protein-coupled receptors (GPCRs) is thought to be universal. However, this paradigm is incompatible with recent reports that the parathyroid hormone (PTH) receptor (PTHR), a crucial GPCR for bone and mineral ion metabolism, sustains G(S) activity and continues to generate cAMP for prolonged periods after ligand washout; during these periods the receptor is observed mainly in endosomes, associated with the bound ligand, G(S) and β-arrestins. In this review we discuss possible molecular mechanisms underlying sustained signaling by the PTHR, including modes of signal generation and attenuation within endosomes, as well as the biological relevance of such non-canonical signaling.

Citing Articles

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The Role of Reversible Phosphorylation of Rhodopsin.

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Altered signaling at the PTH receptor via modified agonist contacts with the extracellular domain provides a path to prolonged agonism in vivo.

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Global longitudinal strain is superior to ejection fraction for detecting myocardial dysfunction in end-stage renal disease with hyperparathyroidism.

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