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.

Communications Biology
|December 1, 2025
PubMed

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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