The Hippo signal transduction network in skeletal and cardiac muscle

• Published in: Science signaling Vol. 7; no. 337; p. re4
• Main Authors: Wackerhage, Henning, Del Re, Dominic P, Judson, Robert N, Sudol, Marius, Sadoshima, Junichi
• Format: Journal Article
• Language: English
• Published: United States 05.08.2014
• Subjects: Acyltransferases; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Heart - embryology; Heart - physiology; Hippo Signaling Pathway; Humans; Models, Molecular; Muscle Development - genetics; Muscle Development - physiology; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology; Myocardium - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Phosphorylation; Protein Serine-Threonine Kinases - chemistry; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Regeneration - physiology; Rhabdomyosarcoma - genetics; Rhabdomyosarcoma - physiopathology; Signal Transduction - genetics; Signal Transduction - physiology; Transcription Factors - genetics; Transcription Factors - metabolism; YAP-Signaling Proteins
• ISSN: 1937-9145
• DOI: 10.1126/scisignal.2005096

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.