ArticleProceedings of the National Academy of Sciences of the United States of America2002
A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 397 citations in OpenAlex.
- Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle.American journal of physiology. Endocrinology and metabolism · 2008Trial
- Treating age-related loss of muscle mass and function: Where should we be focusing?The Journal of physiology · 2026Review
- The hallmarks of skeletal muscle health.Nature metabolism · 2026Review
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- Intricacies of PKB/Akt Activity after Sciatic Nerve Damage: A Comprehensive Review.Current protein & peptide science · 2026Review
- High-Intensity Aerobic Exercise Prevents Angiotensin II-Induced Muscle Atrophy.International neurourology journal · 2025Article
- Skeletal Muscle as a Mediator of Interorgan Crosstalk During Exercise: Implications for Aging and Obesity.Circulation research · 2025Review
- Transcriptional regulation of autophagy in skeletal muscle stem cells.Disease models & mechanisms · 2025Review
- Blood flow restriction training: a new approach for preventing and treating sarcopenia in older adults.Frontiers in physiology · 2025Review
- RNA signaling in skeletal muscle: the central role of microRNAs and exosomal microRNAs.Frontiers in cell and developmental biology · 2025Review
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- Maternal supplementation with mulberry-leaf flavonoids improves the development of skeletal muscle in the offspring of chickens.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- Poly(ADP-Ribose) Polymerases-Inhibitor Talazoparib Inhibits Muscle Atrophy and Fatty Infiltration in a Tendon Release Infraspinatus Sheep Model: A Pilot Study.Metabolites · 2024Article
- Motor neurons and endothelial cells additively promote development and fusion of human iPSC-derived skeletal myocytes.Skeletal muscle · 2024Article
- The Current Landscape of Pharmacotherapies for Sarcopenia.Drugs & aging · 2024Article
- Effect of Zinc Amino Acid Complexes on Growth Performance, Tissue Zinc Concentration, and Muscle Development of Broilers.Biological trace element research · 2024Article
- Effect of synchronicity of amino acid supply on the synthesis of protein in C2C12 myotubes culturedFrontiers in veterinary science · 2024Article
- Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.Physiological reviews · 2023Review
- Article
- Insulin signaling in skeletal muscle during inflammation and/or immobilisation.Intensive care medicine experimental · 2023Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nerve activity controls fiber size and fiber type in skeletal muscle, but the underlying molecular mechanisms remain largely unknown. We have previously shown that Ras-mitogen-activated protein kinase and calcineurin control fiber type but not fiber size in regenerating rat skeletal muscle. Here we report that constitutively active protein kinase B (PKB), also known as Akt, increases fiber size and prevents denervation atrophy in regenerating and adult rat muscles but does not affect fiber type profile. The coexistence of hypertrophic muscle fibers overexpressing activated PKB with normal-size untransfected fibers within the same muscle points to a cell-autonomous control of muscle growth by PKB. The physiological role of this pathway is confirmed by the finding that PKB kinase activity and phosphorylation status are significantly increased in innervated compared with denervated regenerating muscles in parallel with muscle growth. Muscle fiber hypertrophy induced by activated PKB and by a Ras double mutant (RasV12C40) that activates selectively the phosphoinositide 3-kinase-PKB pathway is completely blocked by rapamycin, showing that the mammalian target of rapamycin kinase is the major downstream effector of this pathway in the control of muscle fiber size. On the other hand, nerve activity-dependent growth of regenerating muscle is only partially inhibited by dominant negative PKB and rapamycin, suggesting that other nerve-dependent signaling pathways are involved in muscle growth. The present results support the notion that fiber size and fiber type are regulated by nerve activity through different mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.