title: The Hippo signal transduction network for exercise physiologists.
abstract: 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.
authors.affiliation: School of Medicine, Dentistry and Nutrition, University of Aberdeen, Scotland, UK; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Integrative Physiology, University of Copenhagen, Denmark; and Integrative physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Brendan M
authors.identifier: 0000-0001-6878-8779
authors.initials: BM
authors.lastname: Gabriel
authors.affiliation: School of Sport, University of Stirling, Scotland, UK;
authors.forename: D Lee
authors.initials: DL
authors.lastname: Hamilton
authors.affiliation: Stem Cell Program, Children's Hospital, Boston, Massachusetts; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts; Harvard Stem Cell Institute, Cambridge, Massachusetts;
authors.forename: Annie M
authors.initials: AM
authors.lastname: Tremblay
authors.affiliation: School of Medicine, Dentistry and Nutrition, University of Aberdeen, Scotland, UK; Faculty of Sport and Health Science, Technical University Munich, Germany; henning.wackerhage@tum.de.
authors.forename: Henning
authors.initials: H
authors.lastname: Wackerhage
mesh_terms: D000818:Animals; D015444:Exercise / Q000502:physiology*; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases
keywords: Hippo; Yap; exercise; hypertrophy; skeletal muscle