Gabriel Brendan M, Hamilton D Lee, Tremblay Annie M, Wackerhage Henning
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.
School of Sport, University of Stirling, Scotland, UK;
J Appl Physiol (1985). 2016 May 15;120(10):1105-17. doi: 10.1152/japplphysiol.01076.2015. Epub 2016 Mar 3.
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.
普遍存在的转录共激活因子Yap（基因符号Yap1）和Taz（基因符号Wwtr1）主要通过共激活Tead转录因子来调节基因表达。作为Hippo信号网络的核心，Yap和Taz受Hippo激酶盒调控，此外还受大量与运动相关的信号和信号模块调控。这些包括机械转导、AKT-mTORC1网络、SMAD转录因子、缺氧、葡萄糖稳态、AMPK、通过G蛋白偶联受体的肾上腺素/去甲肾上腺素和血管紧张素II，以及IL-6。因此，运动应会改变多个器官中的Hippo信号，以介导器官对运动特异性适应的至少某些方面。实际上，已表明在肌纤维中过表达Tead1可促进快肌纤维向慢肌纤维类型转变，而在肌纤维和心肌细胞中Yap分别促进骨骼肌肥大和心肌细胞适应。最后，在人类中的全基因组关联研究已将Hippo通路成员LATS2、TEAD1、YAP1、VGLL2、VGLL3和VGLL4与身高联系起来，而身高是体育运动中的一个关键因素。
