Related Experiment Video

Updated: Nov 2, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

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G protein-coupled receptors can control the Hippo/YAP pathway through Gq signaling

Diana Zindel1, Patrick Mensat2, Claire Vol1

  • 1Institut de Génomique Fonctionnelle (IGF), Univ. Montpellier, CNRS, INSERM, Montpellier, France.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|June 11, 2021
PubMed

Insights

The ghrelin receptor activates YAP, a key protein in organ size control, exclusively through the Gq pathway, not G12/13. This discovery offers a novel way to modulate YAP activity for potential therapeutic applications.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • The Hippo pathway regulates organ size and tissue homeostasis.
  • Dysregulation of the Hippo pathway is linked to cancer.
  • G protein-coupled receptors (GPCRs) are increasingly recognized as regulators of the Hippo pathway.

Purpose of the Study:

  • To investigate the role of the ghrelin receptor, a GPCR, in activating the Hippo pathway.
  • To determine the specific G protein signaling pathways involved in ghrelin receptor-mediated YAP activation.
  • To explore the potential of targeting the ghrelin receptor for modulating YAP activity.

Main Methods:

  • Utilized cell-based assays to study GPCR signaling.
  • Investigated the activation of YAP and TAZ transcriptional coactivators.
  • Examined the role of different G protein subtypes (G12/13, Gi/o, Gq) in mediating ghrelin receptor effects.
  • Assessed the impact of ghrelin receptor agonists and antagonists on YAP activity.

Main Results:

  • The ghrelin receptor activates YAP exclusively through the Gq/11 pathway, independent of G12/13.
  • A high basal activity of the ghrelin receptor leads to significant YAP activation.
  • Activating the ghrelin receptor increases YAP activity, while blocking its constitutive activity decreases YAP activity.
  • GPCRs can function as molecular switches to precisely control YAP activity.

Conclusions:

  • The ghrelin receptor acts as a specific Gq-coupled activator of YAP.
  • Targeting the ghrelin receptor offers a novel strategy for modulating YAP activity in a controlled manner.
  • This finding has implications for understanding tissue homeostasis and developing cancer therapies.
Keywords:
Ghrelin receptorHippo pathwaycellular signalingconstitutive activityinverse agonist

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