Related Experiment Video

Updated: Dec 29, 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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LATS suppresses mTORC1 activity to directly coordinate Hippo and mTORC1 pathways in growth control

Wenjian Gan1,2, Xiaoming Dai3, Xiangpeng Dai3

  • 1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. ganw@musc.edu.

Nature Cell Biology
|February 5, 2020
PubMed

Insights

The Hippo pathway

Area of Science:

  • Cellular biology
  • Molecular biology
  • Developmental biology

Background:

  • The Hippo and mTORC1 pathways are critical regulators of organ development.
  • Understanding their interplay is key to controlling growth.
  • Previous research suggested potential connections but lacked direct evidence.

Purpose of the Study:

  • To investigate the crosstalk between the Hippo and mTORC1 signaling pathways.
  • To elucidate the molecular mechanisms coordinating their growth-control functions.
  • To determine how Hippo pathway components regulate mTORC1 activity.

Main Methods:

  • Utilized phosphomimetic knock-in mutant analysis (Raptor-S606D).
  • Employed mouse models (Raptor+/+ vs. RaptorD/D) for in vivo studies.
  • Assessed organ size, cell proliferation, and signaling pathway activation.

Main Results:

  • Hippo pathway kinases (LATS1/2) directly phosphorylate Raptor (mTORC1 component) at S606.
  • This phosphorylation attenuates mTORC1 activation by disrupting Raptor-Rheb interaction.
  • Raptor-S606D mutants and knock-in mice showed reduced cell size, proliferation, and organ size (livers, hearts).
  • Loss of Nf2 or Lats1/2-induced mTORC1 signaling elevation was significantly inhibited in RaptorD/D mice.

Conclusions:

  • Established a direct molecular link between the Hippo and mTORC1 pathways.
  • Demonstrated that Hippo pathway kinases fine-tune mTORC1 activity via Raptor phosphorylation.
  • This crosstalk mechanism plays a crucial role in regulating organ size and development.

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