Non-canonical signaling of the PTH receptor

被引：38

作者：

Vilardaga, Jean-Pierre ^{[1
]}

Gardella, Thomas J. ^{[2
,3
]}

Wehbi, Vanessa L. ^{[1
]}

Feinstein, Timothy N. ^{[1
]}

机构：

[1] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15261 USA

[2] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Boston, MA 02114 USA

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2012年 / 33卷 / 08期

基金：

美国国家卫生研究院;

关键词：

PARATHYROID-HORMONE RECEPTOR; BETA-ADRENERGIC-RECEPTOR; PROTEIN-KINASE-C; PTH/PTHRP RECEPTOR; LIGAND-BINDING; BETA(2)-ADRENERGIC RECEPTORS; BETA-2-ADRENERGIC RECEPTOR; POSTMENOPAUSAL WOMEN; COUPLED RECEPTORS; PEPTIDE LIGANDS;

D O I：

10.1016/j.tips.2012.05.004

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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, Gs and beta-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.

引用

收藏

页码：423 / 431

页数：9

相关论文

共 70 条

[1]

Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis [J].

Antoniucci, Diana M. ;

Sellmeyer, Deborah E. ;

Bilezikian, John P. ;

Palermo, Lisa ;

Ensrud, Kristine E. ;

Greenspan, Susan L. ;

Black, Dennis M. .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2007, 92 (03) :942-947

[2]

The Arrestin Fold: Variations on a Theme [J].

Aubry, Laurence ;

Guetta, Dorian ;

Klein, Gerard .

CURRENT GENOMICS, 2009, 10 (02) :133-142

[3]

A form of Jansen's metaphyseal chondrodysplasia with limited metabolic and skeletal abnormalities is caused by a novel activating parathyroid hormone (PTH)/PTH-related peptide receptor mutation [J].

Bastepe, M ;

Raas-Rothschild, A ;

Silver, J ;

Weissman, I ;

Wientroub, S ;

Jüppner, H ;

Gillis, D .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (07) :3595-3600

[4]

A highly effective dominant negative αs construct containing mutations that affect distinct functions inhibits multiple Gs-coupled receptor signaling pathways [J].

Berlot, CH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (23) :21080-21085

[5]

Parathyroid hormone-related protein: An essential physiological regulator of adult bone mass [J].

Bisello, A ;

Horwitz, MJ ;

Stewart, AF .

ENDOCRINOLOGY, 2004, 145 (08) :3551-3553

[6]

Retrograde transport from endosomes to the trans-Golgi network [J].

Bonifacino, Juan S. ;

Rojas, Raul .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2006, 7 (08) :568-579

[7]

Persistent cAMP-Signals Triggered by Internalized G-Protein-Coupled Receptors [J].

Calebiro, Davide ;

Nikolaev, Viacheslav O. ;

Gagliani, Maria Cristina ;

de Filippis, Tiziana ;

Dees, Christian ;

Tacchetti, Carlo ;

Persani, Luca ;

Lohse, Martin J. .

PLOS BIOLOGY, 2009, 7 (08)

[8]

Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism [J].

Castro, M ;

Nikolaev, VO ;

Palm, D ;

Lohse, MJ ;

Vilardaga, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (44) :16084-16089

[9]

Dual regulation of the parathyroid hormone (PTH)/PTH-related peptide receptor signaling by protein kinase C and β-arrestins [J].

Castro, M ;

Dicker, F ;

Vilardaga, JP ;

Krasel, C ;

Bernhardt, M ;

Lohse, MJ .

ENDOCRINOLOGY, 2002, 143 (10) :3854-3865

[10]

Mechanisms of ligand binding to the parathyroid hormone (PTH)/PTH-related protein receptor:: Selectivity of a modified PTH(1-15) Radioligand for GαS-coupled receptor conformations [J].

Dean, T ;

Linglart, A ;

Mahon, MJ ;

Bastepe, M ;

Jüppner, H ;

Potts, JT ;

Gardella, TJ .

MOLECULAR ENDOCRINOLOGY, 2006, 20 (04) :931-943

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