Evidence map›Paper›PMID 20886089›Full record

ArticlePloS one2010

GPR54 regulates ERK1/2 activity and hypothalamic gene expression in a Gα(q/11) and β-arrestin-dependent manner.

Jacob M Szereszewski, Macarena Pampillo, Maryse R Ahow, Stefan Offermanns, Moshmi Bhattacharya, Andy V Babwah

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 7% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.

  1. Pooled it
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  18. Kisspeptin/Kisspeptin Receptor System in the Ovary.Frontiers in endocrinology · 2017
    Review
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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

6 authors at 3 institutions in 2 countries.

Jacob M SzereszewskiThe Children's Health Research Institute, London, Ontario, Canada.
Macarena Pampillo
Maryse R Ahow
Stefan Offermanns
Moshmi Bhattacharya
Andy V Babwah
Western University · CAChildren’s Health Research Institute · CAMax Planck Institute for Heart and Lung Research · DE

Funding

Canadian Institutes of Health Research MOP81383
6 · The paper itself

Abstract

G protein-coupled receptor 54 (GPR54) is a G(q/11)-coupled 7 transmembrane-spanning receptor (7TMR). Activation of GPR54 by kisspeptin (Kp) stimulates PIP(2) hydrolysis, Ca(2+) mobilization and ERK1/2 MAPK phosphorylation. Kp and GPR54 are established regulators of the hypothalamic-pituitary-gonadal (HPG) axis and loss-of-function mutations in GPR54 are associated with an absence of puberty and hypogonadotropic hypogonadism, thus defining an important role of the Kp/GPR54 signaling system in reproductive function. Given the tremendous physiological and clinical importance of the Kp/GPR54 signaling system, we explored the contributions of the GPR54-coupled G(q/11) and β-arrestin pathways on the activation of a major downstream signaling molecule, ERK, using G(q/11) and β-arrestin knockout mouse embryonic fibroblasts. Our study revealed that GPR54 employs the G(q/11) and β-arrestin-2 pathways in a co-dependent and temporally overlapping manner to positively regulate ERK activity and pERK nuclear localization. We also show that while β-arrestin-2 potentiates GPR54 signaling to ERK, β-arrestin-1 inhibits it. Our data also revealed that diminished β-arrestin-1 and -2 expression in the GT1-7 GnRH hypothalamic neuronal cell line triggered distinct patterns of gene expression following Kp-10 treatment. Thus, β-arrestin-1 and -2 also regulate distinct downstream responses in gene expression. Finally, we showed that GPR54, when uncoupled from the G(q/11) pathway, as is the case for several naturally occurring GPR54 mutants associated with hypogonadotropic hypogonadism, continues to regulate gene expression in a G protein-independent manner. These new and exciting findings add significantly to our mechanistic understanding of how this important receptor signals intracellularly in response to kisspeptin stimulation.

Indexed as

Gene Expression RegulationAnimalsArrestinsbeta-Arrestin 1beta-Arrestin 2beta-ArrestinsCell LineGTP-Binding Protein alpha Subunits, Gq-G11HypothalamusMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Receptors, G-Protein-CoupledReceptors, Kisspeptin-1Arrb1 protein, mouseArrb2 protein, mouseArrestinsbeta-Arrestin 1beta-Arrestin 2beta-ArrestinsGTP-Binding Protein alpha Subunits, Gq-G11Kiss1r protein, mouseMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Receptors, G-Protein-CoupledReceptors, Kisspeptin-1

Identifiers

PMID20886089
PMCPMC2944883
OpenAlexW2066175322

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.