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Study · In vitro (cells) · mouse · 2010

5 results

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

Szereszewski JM, Pampillo M, Ahow MR, Offermanns S, Bhattacharya M, Babwah AV

PloS one23 Sept 2010Cited by 54 (Europe PMC)

PMID20886089 (opens in a new tab)PMCIDPMC2944883 (opens in a new tab)DOI10.1371/journal.pone.0012964 (opens in a new tab)PepBankPUB-20886089
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Summary

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.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Mechanism

    In knockout mouse embryonic fibroblasts, GPR54 used the G(q/11) and beta-arrestin-2 pathways together to positively regulate ERK activity and pERK nuclear localization.

    In plain wordsIn cells, the kisspeptin receptor needed two signalling routes working together to raise ERK activity.

    Peptide
    Kisspeptin-10
    Outcome
    Not applicableERK activity and pERK nuclear localization via Gq/11 and beta-arrestin-2
    Study

    mousen: not reported in source

    Gq/11 and beta-arrestin knockout mouse embryonic fibroblasts
    Outcome group
    Receptor activity and mechanism · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    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.
    2 context sentences
    Summary · context
    These new and exciting findings add significantly to our mechanistic understanding of how this important receptor signals intracellularly in response to kisspeptin stimulation.
    Summary · context
    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.
  2. 02LabIn vitro (cells)Mechanism

    In knockout mouse embryonic fibroblasts, beta-arrestin-2 potentiated GPR54 signalling to ERK.

    In plain wordsIn cells, beta-arrestin-2 increased kisspeptin receptor signalling to ERK.

    Peptide
    Kisspeptin-10
    Outcome
    Not applicableERK signalling potentiation by beta-arrestin-2
    Study

    mousen: not reported in source

    Gq/11 and beta-arrestin knockout mouse embryonic fibroblasts
    Outcome group
    Receptor activity and mechanism · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We also show that while β-arrestin-2 potentiates GPR54 signaling to ERK
    2 context sentences
    Summary · context
    These new and exciting findings add significantly to our mechanistic understanding of how this important receptor signals intracellularly in response to kisspeptin stimulation.
    Summary · context
    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.
  3. 03LabIn vitro (cells)Mechanism

    In knockout mouse embryonic fibroblasts, beta-arrestin-1 inhibited GPR54 signalling to ERK.

    In plain wordsIn cells, beta-arrestin-1 reduced kisspeptin receptor signalling to ERK.

    Peptide
    Kisspeptin-10
    Outcome
    Not applicableERK signalling inhibition by beta-arrestin-1
    Study

    mousen: not reported in source

    Gq/11 and beta-arrestin knockout mouse embryonic fibroblasts
    Outcome group
    Receptor activity and mechanism · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    We also show that while β-arrestin-2 potentiates GPR54 signaling to ERK, β-arrestin-1 inhibits it.
    2 context sentences
    Summary · context
    These new and exciting findings add significantly to our mechanistic understanding of how this important receptor signals intracellularly in response to kisspeptin stimulation.
    Summary · context
    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.
  4. 04LabIn vitro (cells)Mechanism

    In GT1-7 GnRH neuronal cells, reduced beta-arrestin-1 and -2 expression led to distinct patterns of gene expression after Kp-10 treatment.

    In plain wordsIn cells, lowering beta-arrestin levels changed which genes switched on after kisspeptin‑10 treatment, in different patterns for each type.

    Peptide
    Kisspeptin-10
    Outcome
    Not applicableGene expression after Kp-10 with reduced beta-arrestin-1 and -2
    Study

    n: not reported in source

    GT1-7 GnRH hypothalamic neuronal cell line
    Outcome group
    Receptor activity and mechanism · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    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.
    1 context sentence
    Summary · context
    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.
  5. 05LabIn vitro (cells)Mechanism

    When uncoupled from the G(q/11) pathway, GPR54 continued to regulate gene expression in a G protein-independent manner.

    In plain wordsIn cells, the kisspeptin receptor still changed gene activity when its main signalling route was cut off.

    Peptide
    Kisspeptin-10
    Outcome
    Not applicableGene regulation by GPR54 uncoupled from G(q/11)
    Study

    mousen: not reported in source

    Gq/11 and beta-arrestin knockout mouse embryonic fibroblasts and GT1-7 cells
    Outcome group
    Receptor activity and mechanism · Endocrine and hormones
    Studied dose
    Dose not stated

    Source sentences

    Summary
    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.
    2 context sentences
    Summary · context
    These new and exciting findings add significantly to our mechanistic understanding of how this important receptor signals intracellularly in response to kisspeptin stimulation.
    Summary · context
    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.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    10 Oct 2026, 09:43 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

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