Related Experiment Video
Updated: Jun 16, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
The WW domain protein Kibra acts upstream of Hippo in Drosophila
Roland Baumgartner1, Ingrid Poernbacher, Nathalie Buser
1Institute of Molecular Systems Biology, ETH Zürich, Wolfgang-Pauli-Strasse 16, 8093 Zürich, Switzerland.
Insights
Kibra, a WW domain protein, acts upstream of the Hippo kinase pathway, regulating organ size control. It interacts with Merlin and synergizes with Expanded, primarily influencing the Merlin signaling branch.
Area of Science:
- Cell biology
- Molecular biology
- Developmental biology
Background:
- The Hippo kinase pathway is crucial for organ size control and tumor suppression.
- It functions by regulating cell proliferation and apoptosis through a core kinase cascade.
- Upstream regulators of Hippo signaling, particularly for the Merlin branch, are not well understood.
Purpose of the Study:
- To identify novel components upstream of the Hippo kinase pathway.
- To elucidate the regulatory mechanisms of the Merlin signaling branch.
- To understand Kibra's role in Hippo pathway signaling.
Main Methods:
- Investigated the function of the WW domain protein Kibra.
- Analyzed Kibra's interaction with Merlin and Expanded.
- Assessed Kibra's position within the Hippo signaling cascade.
Main Results:
- Identified Kibra as a novel component of the Hippo signaling pathway.
- Demonstrated that Kibra acts upstream of both Hippo and Merlin kinases.
- Showed Kibra physically interacts with Merlin and acts synergistically with Expanded.
- Kibra predominantly regulates the Merlin signaling branch.
Conclusions:
- Kibra is a key upstream regulator in the Merlin-mediated branch of the Hippo pathway.
- Understanding Kibra's function provides new insights into Hippo pathway regulation.
- This finding contributes to the broader understanding of organ size control and tumorigenesis.
Abstract:
The conserved Hippo kinase pathway plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Whereas the function of the core kinase cascade, consisting of the serine/threonine kinases Hippo and Warts, in phosphorylating and thereby inactivating the transcriptional coactivator Yorkie is well established, much less is known about the upstream events that regulate Hippo signaling activity. The FERM domain proteins Expanded and Merlin appear to represent two different signaling branches that feed into the Hippo pathway. Signaling by the atypical cadherin Fat may act via Expanded, but how Merlin is regulated has remained elusive. Here, we show that the WW domain protein Kibra is a Hippo signaling component upstream of Hippo and Merlin. Kibra acts synergistically with Expanded, and it physically interacts with Merlin. Thus, Kibra predominantly acts in the Merlin branch upstream of the core kinase cascade to regulate Hippo signaling.
More Related Videos
Related Concept Videos
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
piRNA - Piwi-interacting RNAs
Hedgehog Signaling Pathway
Hedgehog Signaling Pathway
Canonical Wnt Signaling Pathway

