The Hippo signal transduction network for exercise physiologists

Brendan Gabriel, D. Lee Hamilton, Annie M. Tremblay, Henning Wackerhage

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33 Citations (Scopus)


The ubiquitous transcriptional coactivators Yap (gene symbol Yap1) and Taz (gene symbol Wwtr1) regulate gene expression mainly by coactivating the Tead transcription factors. Being at the center of the Hippo signaling network, Yap and Taz are regulated by the Hippo kinase cassette and additionally by a plethora of exercise-associated signals and signaling modules. These include mechanotransduction, the AKT-mTORC1 network, the SMAD transcription factors, hypoxia, glucose homeostasis, AMPK, adrenaline/epinephrine and angiotensin II through G protein-coupled receptors, and IL-6. Consequently, exercise should alter Hippo signaling in several organs to mediate at least some aspects of the organ-specific adaptations to exercise. Indeed, Tead1 overexpression in muscle fibers has been shown to promote a fast-to-slow fiber type switch, whereas Yap in muscle fibers and cardiomyocytes promotes skeletal muscle hypertrophy and cardiomyocyte adaptations, respectively. Finally, genome-wide association studies in humans have linked the Hippo pathway members LATS2, TEAD1, YAP1, VGLL2, VGLL3, and VGLL4 to body height, which is a key factor in sports.
Original languageEnglish
Pages (from-to)1105-1117
Number of pages13
JournalJournal of applied physiology (Bethesda, Md. : 1985)
Issue number10
Early online date15 May 2016
Publication statusPublished - 15 May 2016

Bibliographical note

B.M. Gabriel is supported by a Wenner-Gren Foundation Postdoctoral Fellowship, a European Foundation for the Study of Diabetes Albert Renold Travel Fellowship, and a Novo Nordisk Foundation Challenge Grant. Work in the Aberdeen Hippo laboratory is funded by Medical Research Council Grant 99477, Sarcoma UK, and Friends of Anchor. A.M. Tremblay is recipient of a postdoctoral fellowship from the Canadian Institutes of Health Research
We are grateful to Prof. Anna Krook (Karolinska Institute), Prof. Jörg Höhfeld (University of Bonn), and Dr. Carsten G. Hansen (University of Edinburgh) for their comments.


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