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Updated: Jan 9, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
KSR1 is a scaffold for the Hippo signaling pathway
Samar Sayedyahossein1, Mohammed Rizwan Babu Sait2, Zhigang Li2
1Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD, USA. samaryahossein@vtc.vt.edu.
Abstract:
The evolutionarily conserved Hippo signaling pathway regulates organ size and tissue homeostasis. Yes-associated protein (YAP) functions as a transcriptional co-activator and is a critical downstream effector of the Hippo signaling pathway. Altered crosstalk with oncogenic signaling pathways contributes to YAP dysregulation in cancer. Kinase Suppressor of Ras 1 (KSR1) scaffolds the Ras cascade. Some of the functions of the Ras and Hippo pathways in regulating cellular processes are similar. Nevertheless, the potential intersection of Ras and Hippo signaling has not been explored. Here, we identify KSR1 as a previously unrecognized scaffold of the Hippo pathway. We demonstrate that KSR1 constitutively binds to YAP and MST1 and forms a complex with LATS1. Moreover, KSR1 modulates YAP protein levels and its transcriptional activity, at least in part through the RhoA/actin axis. Our findings provide insight into the role of KSR1 as a scaffold of the Hippo signaling that could yield novel therapeutics.
Insights
Kinase Suppressor of Ras 1 (KSR1) acts as a novel scaffold for the Hippo signaling pathway, interacting with key proteins like YAP and MST1. This discovery reveals a new regulatory mechanism for YAP, impacting organ size and cancer development.
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Research
Background:
- The Hippo signaling pathway is crucial for organ size and tissue homeostasis.
- Yes-associated protein (YAP) is a key downstream effector of Hippo signaling, and its dysregulation is implicated in cancer.
- The Ras signaling pathway and Hippo pathway share some functional similarities, but their intersection was unexplored.
Purpose of the Study:
- To investigate the potential intersection between the Ras and Hippo signaling pathways.
- To identify novel regulators and mechanisms within the Hippo signaling pathway.
- To explore the role of Kinase Suppressor of Ras 1 (KSR1) in Hippo signaling.
Main Methods:
- Biochemical assays to detect protein-protein interactions.
- Western blotting to assess protein levels.
- Reporter assays to measure transcriptional activity.
- Manipulation of the RhoA/actin axis.
Main Results:
- KSR1 was identified as a previously unrecognized scaffold protein for the Hippo signaling pathway.
- KSR1 constitutively binds to YAP and MST1 and forms a complex with LATS1.
- KSR1 modulates YAP protein levels and transcriptional activity, partly via the RhoA/actin axis.
Conclusions:
- KSR1 serves as a scaffold for the Hippo signaling pathway, linking it to the Ras cascade.
- This interaction provides new insights into YAP regulation and its role in cellular processes.
- The findings suggest KSR1 as a potential therapeutic target for diseases involving YAP dysregulation.
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