ArticleThe Journal of biological chemistry2014
The role of diacylglycerol kinase ζ and phosphatidic acid in the mechanical activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle hypertrophy.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 157 citations in OpenAlex.
- The effects of phosphatidic acid supplementation on strength, body composition, muscular endurance, power, agility, and vertical jump in resistance trained men.Journal of the International Society of Sports Nutrition · 2016Trial
- Potential Influence of Myokines on Skeletal Muscle Tissue Hypertrophy Signaling Pathways: A Narrative Review.Biomolecules · 2026Review
- DGKs in lipid signaling and disease intervention: structural basis, pathological mechanisms, and emerging therapeutic strategies.Cellular & molecular biology letters · 2025Review
- Resistance exercise and skeletal muscle: protein synthesis, degradation, and controversies.European journal of applied physiology · 2025Review
- Piezo1 channels enhance anabolic signaling activation induced by electrical stimulation of cultured myotubes.FEBS open bio · 2025Article
- Skeletal muscle growth to combat diabetes and obesity: the potential role of muscle-secreted factors.Obesity (Silver Spring, Md.) · 2025Review
- Identifying Genetic Predisposition to Dozer Lamb Syndrome: A Semi-Lethal Muscle Weakness Disease in Sheep.Genes · 2025Article
- miRNA-1 regulation is necessary for mechanical overload-induced muscle hypertrophy in male mice.Physiological reports · 2025Article
- Skeletal muscle memory: implications for sports, aging and nutrition.Frontiers in nutrition · 2025Review
- Diacylglycerol kinase δ is required for skeletal muscle development and regeneration.FASEB bioAdvances · 2025Article
- Diacylglycerol kinase γ facilitates the proliferation and migration of neural stem cells in the developing neural tube.Acta biochimica et biophysica Sinica · 2024Article
- Integrative effects of resistance training and endurance training on mitochondrial remodeling in skeletal muscle.European journal of applied physiology · 2024Review
- Molecular aspects of the exercise response and training adaptation in skeletal muscle.Free radical biology & medicine · 2024Review
- Deficiency of diacylglycerol Kinase ζ promotes Beclin1-mediated autophagyInternational journal of medical sciences · 2024Article
- Lipocalin 2 regulates mitochondrial phospholipidome remodeling, dynamics, and function in brown adipose tissue in male mice.Nature communications · 2023Article
- Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.Physiological reviews · 2023Review
- The duration of glucocorticoid treatment alters the anabolic response to high-force muscle contractions.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- Role of Diacylglycerol Kinases in Acute Myeloid Leukemia.Biomedicines · 2023Article
- Article
- The skeletal muscle fiber periphery: A nexus of mTOR-related anabolism.Sports medicine and health science · 2023Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The activation of mTOR signaling is essential for mechanically induced changes in skeletal muscle mass, and previous studies have suggested that mechanical stimuli activate mTOR (mammalian target of rapamycin) signaling through a phospholipase D (PLD)-dependent increase in the concentration of phosphatidic acid (PA). Consistent with this conclusion, we obtained evidence which further suggests that mechanical stimuli utilize PA as a direct upstream activator of mTOR signaling. Unexpectedly though, we found that the activation of PLD is not necessary for the mechanically induced increases in PA or mTOR signaling. Motivated by this observation, we performed experiments that were aimed at identifying the enzyme(s) that promotes the increase in PA. These experiments revealed that mechanical stimulation increases the concentration of diacylglycerol (DAG) and the activity of DAG kinases (DGKs) in membranous structures. Furthermore, using knock-out mice, we determined that the ζ isoform of DGK (DGKζ) is necessary for the mechanically induced increase in PA. We also determined that DGKζ significantly contributes to the mechanical activation of mTOR signaling, and this is likely driven by an enhanced binding of PA to mTOR. Last, we found that the overexpression of DGKζ is sufficient to induce muscle fiber hypertrophy through an mTOR-dependent mechanism, and this event requires DGKζ kinase activity (i.e. the synthesis of PA). Combined, these results indicate that DGKζ, but not PLD, plays an important role in mechanically induced increases in PA and mTOR signaling. Furthermore, this study suggests that DGKζ could be a fundamental component of the mechanism(s) through which mechanical stimuli regulate skeletal muscle mass.
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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.