{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:14:44Z","timestamp":1793236484020,"version":"4.5.0"},"reference-count":56,"publisher":"American Society for Clinical Investigation","issue":"10","license":[{"start":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T00:00:00Z","timestamp":1557964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AR071301"],"award-info":[{"award-number":["R01AR071301"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,16]]},"abstract":"<jats:p>\n                    MAPK signaling consists of an array of successively acting kinases. ERK1 and -2 (ERK1\/2) are major components of the greater MAPK cascade that transduce growth factor signaling at the cell membrane. Here, we investigated ERK1\/2 signaling in skeletal muscle homeostasis and disease. Using mouse genetics, we observed that the muscle-specific expression of a constitutively active MEK1 mutant promotes greater ERK1\/2 signaling that mediates fiber-type switching to a slow, oxidative phenotype with type I myosin heavy chain expression. Using a conditional and temporally regulated Cre strategy, as well as\n                    <jats:italic>Mapk1<\/jats:italic>\n                    (ERK2) and\n                    <jats:italic>Mapk3<\/jats:italic>\n                    (ERK1) genetically targeted mice, MEK1-ERK2 signaling was shown to underlie this fast-to-slow fiber-type switching in adult skeletal muscle as well as during development. Physiologic assessment of these activated MEK1-ERK1\/2 mice showed enhanced metabolic activity and oxygen consumption with greater muscle fatigue resistance. In addition, induction of MEK1-ERK1\/2 signaling increased dystrophin and utrophin protein expression in a mouse model of limb-girdle muscle dystrophy and protected myofibers from damage. In summary, sustained MEK1-ERK1\/2 activity in skeletal muscle produces a fast-to-slow fiber-type switch that protects from muscular dystrophy, suggesting a therapeutic approach to enhance the metabolic effectiveness of muscle and protect from dystrophic disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.127356","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T13:12:13Z","timestamp":1554815533000},"source":"Crossref","is-referenced-by-count":65,"title":["ERK1\/2 signaling induces skeletal muscle slow fiber-type switching and reduces muscular dystrophy disease severity"],"prefix":"10.1172","volume":"4","author":[{"given":"Justin G.","family":"Boyer","sequence":"first","affiliation":[{"name":"Division of Molecular and Cardiovascular Biology, Heart Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio, 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