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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

Tao-1 phosphorylates Hippo/MST kinases to regulate the Hippo-Salvador-Warts tumor suppressor pathway

Julian C Boggiano1, Pamela J Vanderzalm, Richard G Fehon

  • 1Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.

Developmental Cell
|November 15, 2011
PubMed

Insights

The Sterile 20 kinase Tao-1 activates the Hippo pathway, a key regulator of tissue growth. This finding reveals Tao-1

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Molecular Biology

Background:

  • The Hippo-Salvador-Warts (HSW) pathway is crucial for controlling tissue growth.
  • The HSW pathway inhibits growth by phosphorylating and inactivating the oncoprotein Yorkie.
  • Upstream signals that regulate the Hippo kinase remain largely unknown.

Purpose of the Study:

  • To investigate the upstream regulators of the Hippo kinase.
  • To identify novel components of the Hippo-Salvador-Warts pathway.
  • To understand the role of Tao-1 in regulating tissue growth.

Main Methods:

  • Phosphorylation assays to determine Tao-1's effect on Hippo.
  • Analysis of Tao-1 function in developing imaginal epithelia.
  • Investigating conserved mechanisms in mammalian MST kinases.

Main Results:

  • Tao-1 directly phosphorylates the Hippo kinase at T195.
  • Tao-1 restricts cell proliferation in developing epithelia, similar to other HSW pathway genes.
  • Tao-1 mediates upstream signals from Merlin and Expanded, regulating Hippo phosphorylation.

Conclusions:

  • Tao-1 is a key activator of the Hippo kinase within the HSW pathway.
  • The regulatory relationship between Ste20 kinases and Hippo is evolutionarily conserved.
  • Tao-1 is a critical component in the network controlling tissue growth signaling.

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