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Neuregulin 1-activated ERBB4 as a "dedicated" receptor for the Hippo-YAP pathway

Marius Sudol1

  • 1Department of Physiology, National University of Singapore, Laboratory of Cancer Signaling and Domainopathies, Yong Loo Li School of Medicine, Block MD9, 2 Medical Drive 04-01, Singapore 117597, Republic of Singapore. Mechanobiology Institute, T-Lab, 5-01, 5A Engineering Drive 1, Singapore 117411, Republic of Singapore. Institute of Molecular and Cell Biology A*STAR, 61 Biopolis Drive, Proteos, Singapore 138673, Republic of Singapore. phsms@nus.edu.sg.

Science Signaling
|December 11, 2014
PubMed

Insights

Researchers identified neuregulin 1 and its receptor ERBB4 as key activators of the Hippo-YAP pathway, resolving the mystery of its "orphaned" status in mammals. This discovery links EGFR signaling to the Hippo-YAP network, impacting cancer research.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • The Hippo-YAP pathway is crucial for tumor suppression, regulated by cell polarity and junction complexes.
  • Hippo kinases inhibit YAP, a key transcription coactivator.
  • Unlike Drosophila, mammals lacked a known dedicated receptor for the Hippo-YAP pathway.

Purpose of the Study:

  • To identify the missing receptor complex that activates the mammalian Hippo-YAP pathway.
  • To elucidate the upstream regulators of YAP activity in mammals.
  • To understand the interplay between receptor tyrosine kinase signaling and the Hippo-YAP network.

Main Methods:

  • Investigated signaling pathways involving cell polarity and cell-to-cell junctions.
  • Utilized molecular biology techniques to identify receptor-ligand interactions.
  • Focused on the role of neuregulin 1 and ERBB4 in YAP activation.

Main Results:

  • Neuregulin 1 and its receptor ERBB4 were identified as a major complex activating YAP.
  • ERBB4 was confirmed as a dominant receptor for YAP signaling.
  • Established a significant link between the epidermal growth factor receptor (EGFR) signaling axis and the Hippo-YAP network.

Conclusions:

  • The identification of neuregulin 1/ERBB4 resolves the 'orphaned' status of the mammalian Hippo-YAP pathway.
  • ERBB4 acts as a key receptor mediating YAP activation.
  • This finding has significant implications for understanding EGFR-Hippo-YAP signaling crosstalk in cancer biology and therapeutic strategies.

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