ArticleAmerican journal of physiology. Endocrinology and metabolism2014
mTORC1 and JNK coordinate phosphorylation of the p70S6K1 autoinhibitory domain in skeletal muscle following functional overloading.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Protein Phosphorylation Alterations in Myotonic Dystrophy Type 1: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Maternal Diet Quality Is Associated with Placental Proteins in the Placental Insulin/Growth Factor, Environmental Stress, Inflammation, and mTOR Signaling Pathways: The Healthy Start ECHO Cohort.The Journal of nutrition · 2022Trial
- Redox signaling‑mediated muscle atrophy in ACL injury: Role of physical exercise (Review).Molecular medicine reports · 2025Review
- Type 2 diabetes-related sarcopenia: role of nitric oxide.Nutrition & metabolism · 2024Review
- FAS(APO), DAMP, and AKT Phosphoproteins Expression Predict the Development of Nosocomial Infection After Pediatric Burn Injury.Journal of burn care & research : official publication of the American Burn Association · 2024Article
- Network model of skeletal muscle cell signalling predicts differential responses to endurance and resistance exercise training.Experimental physiology · 2024Article
- Advancing cancer cachexia diagnosis with -omics technology and exercise as molecular medicine.Sports medicine and health science · 2024Review
- Salsalate: a pleotropic anti-inflammatory drug in the treatment of diabetes, obesity, and metabolic diseases.Inflammopharmacology · 2023Review
- The emerging role of Piezo1 channels in skeletal muscle physiology.Biophysical reviews · 2023Review
- Mechanisms of mechanical overload-induced skeletal muscle hypertrophy: current understanding and future directions.Physiological reviews · 2023Review
- Effects of Turmeric Extract on Age-Related Skeletal Muscle Atrophy in Senescence-Accelerated Mice.Life (Basel, Switzerland) · 2023Article
- Mechanotransduction for Muscle Protein Synthesis via Mechanically Activated Ion Channels.Life (Basel, Switzerland) · 2023Review
- Understanding the Polyamine and mTOR Pathway Interaction in Breast Cancer Cell Growth.Medical sciences (Basel, Switzerland) · 2022Article
- Repeated and Interrupted Resistance Exercise Induces the Desensitization and Re-Sensitization of mTOR-Related Signaling in Human Skeletal Muscle Fibers.International journal of molecular sciences · 2022Article
- Perturbation of PI3K/Akt signaling affected autophagy modulation in dystrophin-deficient myoblasts.Cell communication and signaling : CCS · 2021Article
- Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions.Genome biology · 2020Article
- PHD1 controls muscle mTORC1 in a hydroxylation-independent manner by stabilizing leucyl tRNA synthetase.Nature communications · 2020Article
- The skeletal muscle fiber: a mechanically sensitive cell.European journal of applied physiology · 2019Review
- Akt/mTOR and AMPK signaling pathways are responsible for liver X receptor agonist GW3965-enhanced gefitinib sensitivity in non-small cell lung cancer cell lines.Translational cancer research · 2019Article
- The Effect of Changing the Contraction Mode During Resistance Training on mTORC1 Signaling and Muscle Protein Synthesis.Frontiers in physiology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The present project was designed to investigate phosphorylation of p70S6K1 in an animal model of skeletal muscle overload. Within 24 h of male Sprague-Dawley rats undergoing unilateral tenotomy to induce functional overloading of the plantaris muscle, phosphorylation of the Thr³⁸⁹ and Thr⁴²¹/Ser⁴²⁴ sites on p70S6K1 was significantly elevated. Since the Thr⁴²¹/Ser⁴²⁴ sites are purportedly mammalian target of rapamycin complex 1 (mTORC1) independent, we sought to identify the kinase(s) responsible for their phosphorylation. Initially, we used IGF-I treatment of serum-deprived HEK-293E cells as an in vitro model system, because IGF-I promotes phosphorylation of p70S6K1 on both the Thr³⁸⁹ and Thr⁴²¹/Ser⁴²⁴ sites in skeletal muscle and in cells in culture. We found that, whereas the mTOR inhibitor TORIN2 prevented the IGF-I-induced phosphorylation of the Thr⁴²¹/Ser⁴²⁴ sites, it surprisingly enhanced phosphorylation of these sites during serum deprivation. JNK inhibition with SP600125 attenuated phosphorylation of the Thr⁴²¹/Ser⁴²⁴ sites, and in combination with TORIN2 both the effect of IGF-I and the enhanced Thr⁴²¹/Ser⁴²⁴ phosphorylation during serum deprivation were ablated. In contrast, both JNK activation with anisomycin and knockdown of the mTORC2 subunit rictor specifically stimulated phosphorylation of the Thr⁴²¹/Ser⁴²⁴ sites, suggesting that mTORC2 represses JNK-mediated phosphorylation of these sites. The role of JNK in mediating p70S6K1 phosphorylation was confirmed in the animal model noted above, where rats treated with SP600125 exhibited attenuated Thr⁴²¹/Ser⁴²⁴ phosphorylation. Overall, the results provide evidence that the mTORC1 and JNK signaling pathways coordinate the site-specific phosphorylation of p70S6K1. They also identify a novel role for mTORC1 and mTORC2 in the inhibition of JNK.
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Registered trials
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