The Hippo signal transduction network in skeletal and cardiac muscle

Henning Wackerhage, Dominic P Del Re, Robert N Judson, Marius Sudol, Junichi Sadoshima

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)


The discovery of the Hippo pathway can be traced back to two areas of research. Genetic screens in fruit flies led to the identification of the Hippo pathway kinases and scaffolding proteins that function together to suppress cell proliferation and tumor growth. Independent research, often in the context of muscle biology, described Tead (TEA domain) transcription factors, which bind CATTCC DNA motifs to regulate gene expression. These two research areas were joined by the finding that the Hippo pathway regulates the activity of Tead transcription factors mainly through phosphorylation of the transcriptional coactivators Yap and Taz, which bind to and activate Teads. Additionally, many other signal transduction proteins crosstalk to members of the Hippo pathway forming a Hippo signal transduction network. We discuss evidence that the Hippo signal transduction network plays important roles in myogenesis, regeneration, muscular dystrophy, and rhabdomyosarcoma in skeletal muscle, as well as in myogenesis, organ size control, and regeneration of the heart. Understanding the role of Hippo kinases in skeletal and heart muscle physiology could have important implications for translational research.

Original languageEnglish
Article numberre4
JournalScience Signaling
Issue number337
Publication statusPublished - 5 Aug 2014

Bibliographical note

Copyright © 2014, American Association for the Advancement of Science.


  • Adaptor Proteins, Signal Transducing
  • Heart
  • Humans
  • Models, Molecular
  • Muscle Development
  • Muscle, Skeletal
  • Myocardium
  • Phosphoproteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Regeneration
  • Rhabdomyosarcoma
  • Signal Transduction
  • Transcription Factors


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