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Updated: Nov 17, 2025
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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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MEKK2 and MEKK3 orchestrate multiple signals to regulate Hippo pathway
Jinqiu Lu1, Zonghao Hu1, Yujie Deng1
1The MOE Key Laboratory of Biosystems Homeostasis and Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, China.
The Journal of Biological Chemistry
|February 11, 2021
Summary
Tumor necrosis factor (TNF) activates the Hippo pathway via MEKK2/3 kinases, inhibiting YAP/TAZ activity. This uncovers a new regulatory mechanism linking Hippo-YAP and NF-κB signaling.
Area of Science:
- Cell biology
- Molecular signaling
- Developmental biology
Background:
- The Hippo pathway regulates organ size by controlling cell proliferation and apoptosis through a kinase cascade.
- Key components include MST1/2, MAP4Ks, LATS1/2, and YAP/TAZ.
- Mechanisms of kinase-mediated Hippo pathway regulation are not fully understood.
Purpose of the Study:
- To elucidate the role of MEKK2/3 in Hippo pathway regulation.
- To investigate the interplay between Hippo-YAP and NF-κB signaling.
- To explore the implications for cerebral cavernous malformations.
Main Methods:
- Investigated TNF-induced Hippo pathway activation.
- Utilized biochemical assays to study protein interactions and phosphorylation.
- Examined the role of MEKK2/3, STRIPAK complex, CCM2, and CCM3.
Main Results:
- TNF activates LATS1/2 and inhibits YAP/TAZ via MEKK2/3.
- MEKK2/3 function parallel to MST1/2 and MAP4Ks in regulating Hippo signaling.
- MEKK2/3 directly phosphorylate LATS1/2 and YAP/TAZ.
- STRIPAK complex inactivates MEKK3, and upstream signals release MEKK3 activity.
Conclusions:
- MEKK2/3 represent a novel regulatory node in the Hippo pathway.
- Discovered a mechanism linking Hippo-YAP and NF-κB signaling.
- Provided insights into the pathogenesis of cerebral cavernous malformations.
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