Program in Molecular Medicine; Davis Lab
Amino Acids, Peptides, and Proteins | Cell Biology | Cellular and Molecular Physiology | Enzymes and Coenzymes | Exercise Physiology | Musculoskeletal System
Skeletal muscle has a remarkable plasticity to adapt and remodel in response to environmental cues, such as physical exercise. Endurance exercise stimulates improvements in muscle oxidative capacity, while resistance exercise induces muscle growth. Here we show that the c-Jun N-terminal kinase (JNK) is a molecular switch that when active, stimulates muscle fibers to grow, resulting in increased muscle mass. Conversely, when muscle JNK activation is suppressed, an alternative remodeling program is initiated, resulting in smaller, more oxidative muscle fibers, and enhanced aerobic fitness. When muscle is exposed to mechanical stress, JNK initiates muscle growth via phosphorylation of the transcription factor, SMAD2, at specific linker region residues leading to inhibition of the growth suppressor, myostatin. In human skeletal muscle, this JNK/SMAD signaling axis is activated by resistance exercise, but not endurance exercise. We conclude that JNK acts as a key mediator of muscle remodeling during exercise via regulation of myostatin/SMAD signaling.
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Copyright © The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
Nat Commun. 2018 Aug 2;9(1):3030. doi: 10.1038/s41467-018-05439-3. Link to article on publisher's site
Lessard SJ, MacDonald TL, Pathak P, Han MS, Coffey VG, Edge J, Rivas DA, Hirshman MF, Davis RJ, Goodyear LJ. (2018). JNK regulates muscle remodeling via myostatin/SMAD inhibition. Open Access Articles. https://doi.org/10.1038/s41467-018-05439-3. Retrieved from https://escholarship.umassmed.edu/oapubs/3558
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This work is licensed under a Creative Commons Attribution 4.0 License.
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