ArticleThe Journal of biological chemistry2011
L-threonine regulates G1/S phase transition of mouse embryonic stem cells via PI3K/Akt, MAPKs, and mTORC pathways.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 78 citations in OpenAlex.
- Stem cell regulation: conserved pluripotency, transcriptional, and metabolic networks in animals and plants.Frontiers in cell and developmental biology · 2026Review
- Metabolic and morphometric analysis of allometric and total liver growth in Post-Hatch chickens.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Prim-O-glucosylcimifugin alleviates influenza virus-induced pneumonia in mice by inhibiting the TGF-β1/PI3KCD/MSK2/RELA signalling pathway.Archives of virology · 2024Article
- Metabolic Profiles of Cancer Stem Cells and Normal Stem Cells and Their Therapeutic Significance.Cells · 2023Review
- Alleviative Effect of Threonine on Cadmium-Induced Liver Injury in Mice.Biological trace element research · 2023Article
- Metabolic control of induced pluripotency.Frontiers in cell and developmental biology · 2023Review
- Integrated metabolomics and transcriptomics to reveal biomarkers and mitochondrial metabolic dysregulation of premature ovarian insufficiency.Frontiers in endocrinology · 2023Article
- L-threonine promotes healthspan by expediting ferritin-dependent ferroptosis inhibition in C. elegans.Nature communications · 2022Article
- L-Proline Supplementation Drives Self-Renewing Mouse Embryonic Stem Cells to a Partially Primed Pluripotent State: The Early Primitive Ectoderm-Like Cell.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Epigenetic Modifications at the Center of the Barker Hypothesis and Their Transgenerational Implications.International journal of environmental research and public health · 2021Review
- Regulation of mTORC1 by amino acids in mammalian cells: A general picture of recent advances.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2021Review
- Review
- Nutrients in the fate of pluripotent stem cells.Cell metabolism · 2021Review
- Review
- Interkingdom Comparison of Threonine Metabolism for Stem Cell Maintenance in Plants and Animals.Frontiers in cell and developmental biology · 2021Review
- Cellular metabolism and homeostasis in pluripotency regulation.Protein & cell · 2020Review
- Physical activity reduces anxiety and regulates brain fatty acid synthesis.Molecular brain · 2020Article
- Energy Metabolism Regulates Stem Cell Pluripotency.Frontiers in cell and developmental biology · 2020Review
- CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis.Stem cell research & therapy · 2019Article
- Amino Acid-Mediated Metabolism: A New Power to Influence Properties of Stem Cells.Stem cells international · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although amino acids can function as signaling molecules in the regulation of many cellular processes, mechanisms surrounding L-threonine involvement in embryonic stem cell (ESC) functions have not been explored. Thus, we investigated the effect of L-threonine on regulation of mouse (m)ESC self-renewal and related signaling pathways. In L-threonine-depleted mESC culture media mRNA of self-renewal marker genes, [(3)H]thymidine incorporation, expression of c-Myc, Oct4, and cyclins protein was attenuated. In addition, resupplying L-threonine (500 μM) after depletion restores/maintains the mESC proliferation. Disruption of the lipid raft/caveolae microdomain through treatment with methyl-β-cyclodextrin or transfection with caveolin-1 specific small interfering RNA blocked L-threonine-induced proliferation of mESCs. Addition of L-threonine induced phosphorylation of Akt, ERK, p38, JNK/SAPK, and mTOR in a time-dependent manner. This activity was blocked by LY 294002 (PI3K inhibitor), wortmannin (PI3K inhibitor), or an Akt inhibitor. L-threonine-induced activation of mTOR, p70S6K, and 4E-BP1 as well as cyclins and Oct4 were blocked by PD 98059 (ERK inhibitor), SB 203580 (p38 inhibitor) or SP 600125 (JNK inhibitor). Furthermore, L-threonine induced phosphorylation of raptor and rictor binding to mTOR was completely inhibited by 24 h treatment with rapamycin (mTOR inhibitor); however, a 10 min treatment with rapamycin only partially inhibited rictor phosphorylation. L-threonine induced translocation of rictor from the membrane to the cytosol/nuclear, which blocked by pretreatment with rapamycin. In addition, rapamycin blocked L-threonine-induced increases in mRNA expressions of trophoectoderm and mesoderm marker genes and mESC proliferation. In conclusion, L-threonine stimulated ESC G(1)/S transition through lipid raft/caveolae-dependent PI3K/Akt, MAPKs, mTOR, p70S6K, and 4E-BP1 signaling pathways.
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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.