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The Hippo size control pathway--ever expanding

Jane I Lin1, Carole L C Poon, Kieran F Harvey

  • 1Cell Growth and Proliferation Laboratory, Peter MacCallum Cancer Centre, 7 St Andrews Place, East Melbourne, Victoria 3002, Australia.

Science Signaling
|January 29, 2013
PubMed

Insights

The Hippo pathway, crucial for organ size and cancer, is regulated by Yes-associated protein (YAP). PTPN14 (Pez) antagonizes YAP, while protease-activated receptors activate it, revealing new regulatory mechanisms.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The Hippo pathway is a critical regulator of organ size and tumorigenesis.
  • The oncoprotein Yes-associated protein (YAP) is a key component of the Hippo pathway, and its regulation is increasingly complex.
  • Understanding YAP regulation is vital for comprehending both normal physiology and disease states.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling the Hippo pathway, specifically focusing on the role of YAP.
  • To identify novel proteins and pathways that interact with and modulate YAP activity.
  • To explore the functional significance of these regulatory interactions in cellular processes and disease.

Main Methods:

  • Utilized Drosophila models to study the in vivo function of Pez (PTPN14) as a repressor of epithelial proliferation.
  • Employed mammalian cell culture systems to examine the interaction between protease-activated receptors and YAP.
  • Investigated the role of PTPN14 (Pez) in antagonizing YAP function by promoting its cytoplasmic localization.

Main Results:

  • PTPN14 (Pez) was identified as an antagonist of YAP, promoting its cytoplasmic localization under conditions of high cell density.
  • In Drosophila, Pez was confirmed to repress epithelial proliferation in vivo.
  • Protease-activated receptors were found to function as activators of YAP in mammalian cells.

Conclusions:

  • These findings reveal intricate regulatory mechanisms governing the Hippo pathway and YAP activity.
  • PTPN14 (Pez) and protease-activated receptors represent newly discovered links in YAP regulation.
  • Further investigation of these regulatory interactions is essential for understanding their roles in physiological and pathological contexts.

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