Evidence map›Paper›PMID 24558046›Full record

ArticleThe Journal of biological chemistry2014

Lipid raft- and protein kinase C-mediated synergism between glucocorticoid- and gonadotropin-releasing hormone signaling results in decreased cell proliferation.

Lancelot Wehmeyer, Andrea Du Toit, Dirk M Lang, Janet P Hapgood

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

16 citing papers in PubMed, 34 citations in OpenAlex.

  1. Trial
  2. Article
  3. The roles of FLOT1 in human diseases (Review).Molecular medicine reports · 2023
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Emerging role of extracellular vesicles in the regulation of skeletal muscle adaptation.Journal of applied physiology (Bethesda, Md. : 1985) · 2019
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Serum and Glucocorticoid Regulated Kinase 1 in Sodium Homeostasis.International journal of molecular sciences · 2016
    Review
  15. Review
  16. 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

4 authors at 2 institutions in 2 countries.

Lancelot WehmeyerFrom the Department of Molecular and Cell Biology, Faculty of Science and.
Andrea Du Toit
Dirk M Lang
Janet P Hapgood
Institute of Molecular and Cell Biology · RUUniversity of Cape Town · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cross-talk between the glucocorticoid receptor (GR) and other receptors is emerging as a mechanism for fine-tuning cellular responses. We have previously shown that gonadotropin-releasing hormone (GnRH) ligand-independently activates the GR and synergistically modulates glucocorticoid-induced transcription of an endogenous gene in LβT2 pituitary gonadotrope precursor cells. Here, we investigated GR and GnRH receptor (GnRHR) cross-talk that involves co-localization with lipid rafts in LβT2 cells. We report that the GnRHR and a small population of the GR co-localize with the lipid raft protein flotillin-1 (Flot-1) at the plasma membrane and that the GR is present in a complex with Flot-1, independent of the presence of ligands. We found that the SGK-1 gene is up-regulated by Dex and GnRH alone, whereas a combination of both ligands resulted in a synergistic increase in SGK-1 mRNA levels. Using siRNA-mediated knockdown and antagonist strategies, we show that the gene-specific synergistic transcriptional response requires the GR, GnRHR, and Flot-1 as well as the protein kinase C pathway. Interestingly, although several GR cofactors are differentially recruited to the SGK-1 promoter in the presence of Dex and GnRH, GR levels remain unchanged compared with Dex treatment alone, suggesting that lipid raft association of the GR has a role in enhancing its transcriptional output in the nucleus. Finally, we show that Dex plus GnRH synergistically inhibit cell proliferation in a manner dependent on SGK-1 and Flot-1. Collectively the results support a mechanism whereby GR and GnRHR cross-talk within Flot-1-containing lipid rafts modulates cell proliferation via PKC activation and SGK-1 up-regulation.

Indexed as

AnimalsCell ProliferationChlorocebus aethiopsCOS CellsDexamethasoneDrug SynergismGene Expression Regulation, EnzymologicGlucocorticoidsGonadotropin-Releasing HormoneImmediate-Early ProteinsMembrane MicrodomainsMembrane ProteinsMiceProtein Kinase CProtein Serine-Threonine KinasesReceptors, GlucocorticoidDexamethasoneflotillinsGlucocorticoidsGonadotropin-Releasing HormoneImmediate-Early ProteinsMembrane ProteinsProtein Kinase CProtein Serine-Threonine KinasesReceptors, GlucocorticoidReceptors, LHRHSerum-Glucocorticoid Regulated KinasesCell ProliferationFlotillin-1Gene RegulationGlucocorticoid ReceptorGlucocorticoidsGnRH ReceptorLipid RaftsProtein Kinase C (PKC)SGK-1Synergism

Identifiers

PMID24558046
PMCPMC3974992
OpenAlexW2091774186

What OpenQuestion holds

Textmetadata
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.