Evidence map›Paper›PMID 21713996›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2011

Parathyroid hormone signaling via Gαs is selectively inhibited by an NH(2)-terminally truncated Gαs: implications for pseudohypoparathyroidism.

Svetlana Puzhko, Cynthia Gates Goodyer, Mohammad Amin Kerachian, Lucie Canaff, Madhusmita Misra, Harald Jüppner, Murat Bastepe, Geoffrey N Hendy

Abstract read
In one paragraph

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 42 citations in OpenAlex.

  1. Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016
    Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Molecular Definition of Pseudohypoparathyroidism Variants.The Journal of clinical endocrinology and metabolism · 2021
    Review
  8. A Novel GNAS Duplication Associated With Loss-of-Methylation Restricted to Exon A/B Causes Pseudohypoparathyroidism Type Ib (PHP1B).Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021
    Article
  9. Observational
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. A Large Inversion Involving GNAS Exon A/B and All Exons Encoding Gsα Is Associated With Autosomal Dominant Pseudohypoparathyroidism Type Ib (PHP1B).Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017
    Article
  16. Pseudohypoparathyroidism: one gene, several syndromes.Journal of endocrinological investigation · 2017
    Review
  17. Nonclassic features of pseudohypoparathyroidism type 1A.Current opinion in endocrinology, diabetes, and obesity · 2017
    Review
  18. Article
  19. GNAS Spectrum of Disorders.Current osteoporosis reports · 2015
    Review
  20. Loss of methylation at GNAS exon A/B is associated with increased intrauterine growth.The Journal of clinical endocrinology and metabolism · 2015
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Svetlana PuzhkoEndocrine Research Laboratory, McGill University, Montreal, Quebec, Canada.
Cynthia Gates Goodyer
Mohammad Amin Kerachian
Lucie Canaff
Madhusmita Misra
Harald Jüppner
Murat Bastepe
Geoffrey N Hendy
Harvard University · USMcGill University · CARoyal Victoria Hospital · CAVictoria Hospital · CA

Funding

XLas Relative to Gsa in Bone and Mineral Ion MetabolismR01DK073911 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BASTEPE, MURAT · 2007 to 2020
$4.9M
Molecular Definition of PseudohypoparathyroidismR37DK046718 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI JUEPPNER, HARALD W. · 2002 to 2011
$4.0M
CIHRNIDDK NIH HHS R01 DK073911NIDDK NIH HHS R37 DK046718NIDDK NIH HHS R37 DK46718
6 · The paper itself

Abstract

Pseudohypoparathyroid patients have resistance predominantly to parathyroid hormone (PTH), and here we have examined the ability of an alternative Gαs-related protein to inhibit Gαs activity in a hormone-selective manner. We tested whether the GNAS exon A/B-derived NH(2)-terminally truncated (Tr) αs protein alters stimulation of adenylate cyclase by the PTH receptor (PTHR1), the thyroid-stimulating hormone (TSH) receptor (TSHR), the β(2)-adrenergic receptor (β(2)AR), or the AVP receptor (V2R). HEK293 cells cotransfected with receptor and full-length (FL) Gαs ± Tr αs protein expression vectors were stimulated with agonists (PTH [10(-7) to 10(-9)  M], TSH [1 to 100 mU], isoproterenol [10(-6) to 10(-8)  M], or AVP [10(-6) to 10(-8)  M]). Following PTH stimulation, HEK293 cells cotransfected with PTHR1 + FL Gαs + Tr αs had a significantly lower cAMP response than those transfected with only PTHR1 + FL Gαs. Tr αs also exerted an inhibitory effect on the cAMP levels stimulated by TSH via the TSHR but had little or no effect on isoproterenol or AVP acting via β(2)AR or V2R, respectively. These differences mimic the spectrum of hormone resistance in pseudohypoparathyroidism type 1a (PHP-1a) and type 1b (PHP-1b) patients. In opossum kidney (OK) cells, endogenously expressing the PTHR1 and β(2)AR, the exogenous expression of Tr αs at a level similar to endogenous FL Gαs resulted in blunting of the cAMP response to PTH, whereas that to isoproterenol was unaltered. A pseudopseudohypoparathyroid patient with Albright hereditary osteodystrophy harbored a de novo paternally inherited M1I Gαs mutation. Similar maternally inherited mutations at the initiation codon have been identified previously in PHP-1a patients. The M1I αs mutant (lacking the first 59 amino acids of Gαs) blunted the increase in cAMP levels stimulated via the PTHR1 in both HEK293 and OK cells similar to the Tr αs protein. Thus NH(2)-terminally truncated forms of Gαs may contribute to the pathogenesis of pseudohypoparathyroidism by inhibiting the activity of Gαs itself in a GPCR selective manner.

Indexed as

Signal TransductionBlotting, WesternCell LineCyclic AMPGTP-Binding ProteinsHumansParathyroid HormonePseudohypoparathyroidismCyclic AMPGTP-Binding ProteinsParathyroid Hormone

Identifiers

PMID21713996
PMCPMC3916968
OpenAlexW2016686236

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.