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Updated: Apr 4, 2026

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

Published on: September 13, 2018

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Identification of Happyhour/MAP4K as Alternative Hpo/Mst-like Kinases in the Hippo Kinase Cascade

Yonggang Zheng1, Wei Wang1, Bo Liu1

  • 1Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Developmental Cell
|September 15, 2015
PubMed

Insights

The Hippo pathway regulates cell growth. Researchers discovered a new kinase, Happyhour (Hppy)/MAP4K, that works with Hpo/Mst to control Yki/YAP localization via the cytoskeleton.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • The Hippo kinase cascade, involving Hpo/Mst, Wts/Lats, and Yki/YAP/TAZ, regulates cell proliferation and organ size.
  • The precise mechanisms linking Yki/YAP/TAZ activity to the actin cytoskeleton remain unclear and debated.

Purpose of the Study:

  • To elucidate the mechanisms of cytoskeleton-mediated regulation of Yki/YAP/TAZ.
  • To identify novel kinases involved in the Hippo pathway signaling.

Main Methods:

  • Utilized Drosophila imaginal discs as an in vivo model system.
  • Conducted a systematic genetic screen to identify key regulators.
  • Investigated the phosphorylation of Wts/Lats by Hppy/MAP4K and its functional consequences.

Main Results:

  • Demonstrated that Wts, not Hpo, is essential for cytoskeleton-dependent Yki localization in Drosophila.
  • Identified Happyhour (Hppy) and its mammalian homologs MAP4K1/2/3/5 as novel kinases that phosphorylate Wts/Lats.
  • Showed that combined loss of Hpo/Mst and Hppy/MAP4K disrupts Yki/YAP localization and YAP translocation during contact inhibition.

Conclusions:

  • Wts is indispensable for cytoskeleton-mediated Yki regulation.
  • Hppy/MAP4K kinases function redundantly with Hpo/Mst to activate Wts/Lats.
  • These findings expand the understanding of the Hippo kinase cascade's regulation by the cytoskeleton.

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