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Updated: May 13, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
Okadaic Acid: a tool to study the hippo pathway
Yutaka Hata1, Shikshya Timalsina, Sainawaer Maimaiti
1Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113-8519, Japan. yuhammch@tmd.ac.jp
Abstract:
Mammalian Ste20-like kinases 1 and 2 (MST1 and MST2) are activated in NIH3T3 cells exposed to okadaic acid. The Hippo pathway is a newly emerging signaling that functions as a tumor suppressor. MST1 and MST2 work as core kinases of the Hippo pathway and their activities depend on the autophosphorylation, which is negatively regulated by protein phosphatase 2A (PP2A). Okadaic acid has been frequently used to enhance the phosphorylation of MST1 and MST2 and to trigger the activation of the Hippo pathway. However other components of the Hippo pathway could also be targets of okadaic acid. In this review we first briefly summarize the molecular architecture of the Hippo pathway for the reference of researchers outside the field. We explain how MST kinases are regulated by PP2A and how okadaic acid activates MST2. Thereafter we discuss which components of the Hippo pathway are candidate substrates of protein phosphatases and which points we need to consider in the usage of okadaic acid to study the Hippo pathway.
Insights
Okadaic acid activates the Hippo pathway by enhancing MST1/MST2 kinase phosphorylation, a key tumor suppressor pathway. Researchers should consider other phosphatase targets when using okadaic acid to study the Hippo pathway.
Area of Science:
- Cell biology
- Molecular signaling
- Cancer research
Background:
- The Hippo pathway is a critical tumor suppressor signaling network.
- Mammalian Ste20-like kinases (MST1 and MST2) are core kinases regulating the Hippo pathway.
- Protein phosphatase 2A (PP2A) negatively regulates MST1/MST2 activity via dephosphorylation.
Purpose of the Study:
- To review the molecular architecture of the Hippo pathway.
- To explain the regulation of MST kinases by PP2A.
- To discuss the impact of okadaic acid on Hippo pathway components.
Main Methods:
- Review of existing literature on the Hippo pathway.
- Analysis of MST kinase regulation by PP2A.
- Discussion of okadaic acid's effects on Hippo pathway signaling.
Main Results:
- Okadaic acid enhances MST1 and MST2 phosphorylation, activating the Hippo pathway.
- MST1 and MST2 activities are regulated by autophosphorylation and PP2A.
- Other Hippo pathway components may also be targets of okadaic acid-sensitive phosphatases.
Conclusions:
- Okadaic acid is a tool to activate the Hippo pathway, but its effects may extend beyond MST kinases.
- Careful consideration is needed when using okadaic acid to study the Hippo pathway.
- Identifying additional phosphatase targets is crucial for understanding Hippo pathway regulation.
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