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Updated: Mar 17, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
Ack promotes tissue growth via phosphorylation and suppression of the Hippo pathway component Expanded
Lianxin Hu1, Jiajun Xu1, Meng-Xin Yin1
1State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
Abstract:
Non-receptor tyrosine kinase activated cdc42 kinase was reported to participate in several types of cancers in mammals. It is also believed to have an anti-apoptotic function in Drosophila. Here, we report the identification of Drosophila activated cdc42 kinase as a growth promoter and a novel Hippo signaling pathway regulator. We find that activated cdc42 kinase promotes tissue growth through modulating Yorkie activity. Furthermore, we demonstrate that activated cdc42 kinase interacts with Expanded and induces tyrosine phosphorylation of Expanded on multiple sites. We propose a model that activated cdc42 kinase negatively regulates Expanded by changing its phosphorylation status to promote tissue growth. Moreover, we show that ack genetically interacts with merlin and expanded. Thus, we identify Drosophila activated cdc42 kinase as a Hippo pathway regulator.
Insights
Activated Cdc42 kinase promotes tissue growth in Drosophila by regulating the Hippo pathway. This kinase interacts with Expanded, influencing its phosphorylation and activity to drive growth.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Non-receptor tyrosine kinase activated Cdc42 kinase (ACK) is implicated in mammalian cancers.
- ACK is known to possess anti-apoptotic functions in Drosophila.
Purpose of the Study:
- To identify the role of Drosophila ACK in tissue growth.
- To investigate ACK's function as a regulator of the Hippo signaling pathway.
Main Methods:
- Genetic interaction studies in Drosophila.
- Analysis of protein-protein interactions between ACK and Hippo pathway components.
- Phosphorylation site mapping of Expanded.
Main Results:
- Drosophila ACK functions as a potent tissue growth promoter.
- ACK modulates Yorkie activity, a key downstream effector of the Hippo pathway.
- ACK directly interacts with Expanded, inducing its tyrosine phosphorylation.
- ACK negatively regulates Expanded by altering its phosphorylation status.
- ACK exhibits genetic interactions with merlin and Expanded.
Conclusions:
- Drosophila ACK is identified as a novel regulator of the Hippo signaling pathway.
- ACK promotes tissue growth by negatively regulating Expanded and modulating Yorkie activity.
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